Referto Analisi : GeneScreen - Analisi Malattie Ereditarie mediante sequenziamento NGS

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1 B54378 Referto Analisi : GeneScreen - Analisi Malattie Ereditarie mediante sequenziamento NGS Data Referto:23/10/2015 Ora:12:39 Anagrafica Laboratorio / Medico Centro Inviante: Città: Anagrafica Paziente Cognome: Data di Nascita: Origine Etnica: N.A. Medico inviante: Indicazione: Storia Clinica: Nome: Luogo di Nascita: Sesso: Vs. Codice di riferimento: Dati Campione Tipo Campione: Data Accettazione: Prelievo Ematico Ns. Codice campione: B /10/2015 Ora Accettazione: 19:42 Data prelievo: Dati Analisi Analisi effettuata/e: GeneScreen - Analisi Malattie Ereditarie mediante sequenziamento NGS Codice OMIM: Ereditarietà: Gene investigato: OMIM: Sequenza riferimento: Metodo di analisi: Next Generation Sequencing (NGS) Strategia diagnostica: Data inizio analisi: 05/10/2015 Data fine analisi: 23/10/2015 Pagina 1 di 2

2 B54378 Risultati e Conclusioni Risultato: - gene TGM1 (Ichthyosis, lamellar): Presenza della mutazione V518M (c.1552 G>A) in eterozigosi.[rs ] - gene NPC2 (Niemann-Pick type C2 disease): Presenza della mutazione V30M (c.88 G>A) in eterozigosi.[rs ] Interpretazione: Il campione in esame presenta le mutazioni: V518M (c.1552 G>A) in ETEROZIGOSI a livello del gene TGM1. Ref:Hennies (1998) Am J Hum Genet 62, 1052 Note tecniche: Commenti: Suggerimenti: Risultati verificati da: Risultati validati da: V30M (c.88 G>A) in ETEROZIGOSI a livello del gene NPC2. Ref:Park (2003) Hum Mutat 22, 313 Relazione tecnica in allegato L'esame effettuato ha prodotto un risultato per il quale è consigliabile un colloquio di approfondimento con uno specialista in genetica medica. Giuliano Cottone Data verifica : 21/10/2015 Francesco Fiorentino Data validazione : 23/10/2015 Il presente referto costituisce copia conforme all'originale, il quale è depositato negli archivi del laboratorio Genoma Group Srl. Il Genetista Dr.ssa Marina Baldi Il Direttore del laboratorio Dr. Francesco Fiorentino Genoma Group Srl Genoma Group Srl Roma, 23 ottobre 2015 Pagina 2 di 2

3 Pagina 1 / 41 Relazione tecnica GeneScreen Analisi multipla di 724 malattie genetiche ereditarie

4 Pagina 2 / 41 PROSPETTO DELL'ANALISI Paziente Tipo Campione Codice Campione Metodo Analisi Prelievo Ematico B54378 Next Generation Sequencing (NGS) GeneScreen - Analisi Malattie Ereditarie mediante sequenziamento NGS Conclusioni - gene TGM1 (Ichthyosis, lamellar): Presenza della mutazione V518M (c.1552 G>A) in eterozigosi.[rs ] - gene NPC2 (Niemann-Pick type C2 disease): Presenza della mutazione V30M (c.88 G>A) in eterozigosi.[rs ] La genomica di nuova generazione Negli ultimi anni, gli straordinari progressi conseguiti nel settore della genomica e delle biotecnologie hanno posto le basi per leggere e comprendere le informazioni contenute nel nostro DNA, il genoma. In particolare le nuove tecnologie di sequenziamento, Next Generation Sequencing (NGS), ci permettono oggi di accedere alla sequenza del nostro DNA in modo più facile ed efficace, fornendo una valutazione approfondita dell informazione genetica di ogni singolo individuo. Ogni persona nasce, infatti, con caratteristiche genetiche che la differenziano dagli altri e che la rendono unica. Mentre la maggior parte delle differenze nella sequenza del DNA tra persone diverse è innocua, alcuni cambiamenti, definiti mutazioni genetiche, possono alterare la funzionalità genomica e rendere quella persona portatrice di una specifica malattia genetica trasmissibile ai propri figli. I portatori di malattie genetiche sono tipicamente individui sani, completamente privi di sintomi ed inconsapevoli di essere a rischio di trasmettere tale errore del DNA ai figli.

5 Pagina 3 / 41 Il test GeneScreen GeneScreen è un test diagnostico, sviluppato da GENOMA Group, che permette di eseguire un analisi multipla di oltre 700 malattie genetiche ereditarie, tra cui quelle più frequenti nella popolazione italiana, come la Fibrosi Cistica, l Anemia Falciforme, la Talassemia, la Sordità Ereditaria, etc. GeneScreen consente alla coppia di conoscere, attraverso l analisi del loro DNA, se si è portatori di gravi malattie genetiche. Il test, quindi, permette di identificare le coppie a rischio di trasmettere ai loro figli una specifica malattia genetica. Indicazioni al test GeneScreen GeneScreen è indicato: Per le coppie che progettano di diventare genitori, sia tramite concepimento naturale che mediante l accesso a tecniche di procreazione medicalmente assistita (PMA); Per le coppie che sono in attesa di un figlio, e che desiderano ridurre il rischio di trasmettere a quest ultimo una malattia genetica ereditaria; Per le coppie che fanno ricorso a tecniche di fecondazione eterologa, al fine di individuare un donatore di gameti che non sia portatore di mutazioni nei medesimi geni riscontrate in uno dei partners della coppia. L esame può essere effettuato su un singolo individuo o, preferibilmente, su entrambi i partners della coppia. Come viene effettuato il test GeneScreen? Il test viene eseguito mediante il prelievo di un campione ematico. Tramite un analisi complessa di laboratorio, Il DNA viene isolato dalle cellule nucleate ed amplificato mediante tecnica PCR.. Successivamente, attraverso un processo tecnologico avanzato di sequenziamento massivo parallelo (MPS), che impiega tecniche di Next Generation Sequencing (NGS) utilizzando sequenziatori ILLUMINA, si sequenziano completamente 550 geni (esoni e regioni introniche adiacenti, ± 5 nucleotidi)(tabella 1) ad elevata profondità di lettura. Le sequenze geniche ottenute vengono analizzate attraverso un avanzata analisi bioinformatica, per determinare la presenza di eventuali mutazioni nei geni in esame. I geni elencati in Tabella 1, sono stati selezionati in base all incidenza nella popolazione delle malattie causate da mutazioni in tali geni, alla gravità del fenotipo clinico alla nascita ed all importanza del quadro patogenetico associato, seguendo le indicazioni dell American College of Medical Genetics (ACMG)(Grody et al., Genet Med 2013:15: ).

6 Pagina 4 / 41 Risultati ottenibili con il test GeneScreen POSITIVO Presenza di una o più mutazioni: indica che il test ha rilevato una o più mutazioni a livello di uno (o più) geni. Il nostro genetista, in sede di consulenza genetica, spiegherà in maniera dettagliata il significato del risultato del test ed, eventualmente, prospetterà la necessità di estendere l esame all altro partner della coppia, al fine di verificare che quest ultimo non sia portatore delle medesima malattia genetica, nel qual caso si ravviserebbe un rischio di trasmissione della patologia ai figli. Le mutazioni riscontrabili tramite il test GeneScreen possono rientrare nelle seguenti categorie prognostiche: con significato patologico noto; con significato benigno in quanto sono riscontrabili in individui normali e sono prive di significato patologico; con significato incerto in quanto non ancora note o caratterizzate dalla comunità medicoscientifica. Se entrambi i partners della coppia dovessero risultare positivi per il test, portatori di una mutazione con significato patologico noto nel medesimo gene, il nostro genetista potrà fornire una panoramica sulle opzioni diagnostiche attualmente disponibili per verificare lo stato di salute del feto, in caso di futura gravidanza. NEGATIVO - Assenza di mutazioni: indica che il test non ha rilevato la presenza di mutazioni nei geni esaminati. Parametri utilizzati per la refertazione delle varianti genetiche L analisi è mirata esclusivamente ai geni elencati in Tabella 1. Verranno refertate solo le mutazioni classificate come a significato patogenetiche noto o con significato incerto, sulla base dei dati della letteratura scientifica e la classificazione presente nel database di riferimento Human Gene Mutation Database (HGMD), aggiornato alla data del prelievo. Inoltre, seguendo le indicazioni dell American College of Medical Genetics (ACMG), sono state considerate come patogenetiche o presunte patogenetiche solo le mutazioni con un valore di Minor Allele Frequency (MAF) <5% (1000 Genomes Project), riferibile come la frequenza di ricorrenza dell allele meno comune all interno della popolazione. Target Coverage Si intende per Target Coverage, il numero medio di letture (reads) ottenute dal sequenziamento per ciascuna base nucleotidica costituente il gene. Le varianti con una profondità di lettura

7 Pagina 5 / 41 (numero di reads) inferiore a 30X non sono vengono evidenziate dall algoritmo di analisi bioinformatica. Accuratezza del test GeneScreen Le tecniche attuali di sequenziamento del DNA producono risultati con un accuratezza superiore al 99%. Benché questo test sia molto accurato bisogna sempre considerare i limiti dell esame, di seguito descritti. Limiti del test GeneScreen Questo esame valuta solo le malattie genetiche ed i geni elencati in Tabella 1. Il test non evidenzia altre malattie genetiche o geni non specificamente investigati. L esame inoltre non è in grado di evidenziare: mutazioni localizzate nelle regioni introniche oltre ± 5 nucleotidi dai breakpoints; delezioni, inversioni o duplicazioni maggiori di 20 bp; mosaicismi della linea germinale (cioè mutazioni presenti solo nei gameti). Un risultato NEGATIVO - Assenza di mutazioni per i geni investigati non esclude la possibilità di essere portatori di una mutazione localizzata in una regione del genoma non investigata dall esame. E possibile che alcune zone del proprio DNA non possano essere sequenziate o che abbiano una copertura inferiore ai limiti fissati dagli esperti di GENOMA Group per garantire un analisi accurata delle varianti. Queste regioni non saranno quindi comprese nell analisi qualora non superino gli standard qualitativi richiesti. In alcuni casi, il risultato di un analisi genomica può rivelare una variante o mutazione del DNA con un significato clinico non certo o determinabile in base alle attuali conoscenze medicoscientifiche. L interpretazione delle varianti genetiche si basa sulle più recenti conoscenze disponibili al momento dell analisi. Tale interpretazione potrebbe cambiare in futuro con l acquisizione di nuove informazioni scientifiche e mediche sulla struttura del genoma ed influire sulla valutazione stessa delle varianti. Alcune patologie possono essere causate o regolate da più di una variante nel suo DNA in uno o più geni. Alcune di queste varianti possono non essere ancora state identificate o validate dalla comunità scientifica e quindi non essere riportate come patogenetiche al momento dell analisi.

8 Pagina 6 / 41 Limite intrinseco della metodologia NGS utilizzata è la mancanza di uniformità di coverage per ciascuna regione genica analizzata. Tale limite si traduce nella possibilità, insita nelle metodiche NGS, che specifiche mutazioni dei geni selezionati potrebbero non essere state rilevate dal test. Tabella 1: GeneScreen - Elenco dei geni analizzati e della malattie genetiche investigate DISEASE NAME PhenoMIM GENE 1 17-alpha-hydroxylase/17,20-lyase CYP17A beta-hydroxysteroid dehydrogenase X HSD17B beta-hydroxysteroid dehydrogenase, type II, HSD3B2 4 3-hydroxy-3-methylglutaric aciduria HMGCL 5 3-methylglutaconic aciduria type AUH 6 3-methylglutaconic aciduria type OPA3 7 46XY sex reversal NR5A1 8 4-hydroxybutyric aciduria ALDH5A1 9 Aarskog-Scott syndrome FGD1 10 ABCD syndrome EDNRB 11 Achalasia-addisonianismalacrimia syndrome AAAS 12 Achondrogenesis type 1B SLC26A2 13 Acyl-CoA dehydrogenase ACAD9 14 Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase CYP11B1 15 Adrenal insufficiency, congenital, with 46XY sex reversal, partial or CYP11A1 complete 16 Adrenocortical insufficiency NR5A1 17 Adrenoleukodystrophy ABCD1 18 Adult neuronal ceroid lipofuscinosis PPT1

9 Pagina 7 / Adult neuronal ceroid lipofuscinosis CTSD 20 Adult neuronal ceroid lipofuscinosis 4A CLN6 21 Aicardi-Goutières syndrome TREX1 22 Aicardi-Goutieres syndrome RNASEH2B 23 Aicardi-Goutieres syndrome RNASEH2C 24 Aicardi-Goutieres syndrome RNASEH2A 25 Aicardi-Goutieres syndrome SAMHD1 26 Aldosteronism, glucocorticoidremediable CYP11B1 27 Allan-Herndon-Dudley syndrome SLC16A2 28 Alpers syndrome POLG 29 Alpha-methylacyl-Coa Racemase AMACR 30 Alpha-thalassemia HBA1 31 Alpha-thalassemia myelodysplasia syndrome, ATRX somatic 32 Alpha-thalassemia/mental retardation syndrome ATRX 33 Alport syndrome COL4A5 34 Alport syndrome autosomal recessive (gene COL4A3) COL4A3 35 Alport syndrome autosomal recessive (gene COL4A4) COL4A4 36 Alström syndrome ALMS1 37 Amish infantile epilepsy syndrome ST3GAL5 38 Amyotrophic lateral sclerosis 2, juvenile ALS2 39 Anauxetic dysplasia RMRP 40 Angelman syndrome UBE3A 41 Antenatal Bartter syndrome KCNJ1 42 Antenatal Bartter syndrome type SLC12A1

10 Pagina 8 / Antley-Bixler syndrome with genital anomalies and disordered POR steroidogenesis 44 Aplasia/hypoplasia of limbs and pelvis WNT7A 45 Aplastic anemia NBN 46 Apparent mineralocorticoid excess HSD11B2 47 Argininosuccinic aciduria ASL 48 Aromatic L-amino acid decarboxylase DDC 49 Arthrogryposis - renal dysfunction - cholestasis VPS33B 50 Arthrogryposis, renal dysfunction, and cholestasis VIPAR 51 Ataxia - oculomotor apraxia type APTX 52 Ataxia with vitamin E TTPA 53 Ataxia-telangiectasia ATM 54 Atelosteogenesis type II SLC26A2 55 Autism, susceptibility to, X-linked RPL10 56 Autoimmune lymphoproliferative syndrome, type IA FAS 57 Autoimmune lymphoproliferative syndrome, type IB FASLG 58 Autoimmune lymphoproliferative syndrome, type II CASP10 59 Autoimmune polyendocrinopathy syndrome, type I, with or without AIRE reversible metaphyseal dysplasia 60 Autosomal dominant Charcot- Marie-Tooth disease type 2K GDAP1 61 Autosomal recessive ataxia due to ubiquinone ADCK3

11 Pagina 9 / Autosomal recessive Charcot- Marie-Tooth disease with hoarseness Autosomal recessive distal spinal muscular atrophy type 4 Autosomal recessive doparesponsive dystonia Autosomal recessive hypophosphatemic rickets 1 Autosomal recessive hypophosphatemic rickets 2 Autosomal recessive intermediate Charcot-Marie-Tooth disease type A Autosomal recessive limb-girdle muscular dystrophy type 2I Autosomal recessive limb-girdle muscular dystrophy type 2M Autosomal recessive limb-girdle muscular dystrophy type C Autosomal recessive limb-girdle muscular dystrophy type C Autosomal recessive limb-girdle muscular dystrophy type C Autosomal recessive malignant osteopetrosis 1 Autosomal recessive malignant osteopetrosis 4 Autosomal recessive nonsyndromic sensorineural deafness type DFNB12 Autosomal recessive nonsyndromic sensorineural deafness type DFNB GDAP PLEKHG TH DMP ENPP GDAP FKRP FKTN POMGNT POMT POMT TCIRG CLCN CDH USH1C

12 Pagina 10 / Autosomal recessive nonsyndromic sensorineural deafness type DFNB1A (gene GJB2 GJB2) 78 Autosomal recessive nonsyndromic sensorineural MYO7A deafness type DFNB2 79 Autosomal recessive polycystic kidney disease PKHD1 80 Autosomal recessive progressive external ophthalmoplegia POLG 81 Autosomal recessive spastic ataxia of Charlevoix-Saguenay SACS 82 Autosomal recessive spondylocostal dysostosis DLL3 83 Bannayan-Riley-Ruvalcaba syndrome PTEN 84 Barth syndrome TAZ 85 Becker muscular dystrophy DMD 86 Beckwith-Wiedemann syndrome NSD1 87 Beta-thalassemia HBB 88 Bethlem myopathy COL6A1 89 Bethlem myopathy COL6A2 90 Bethlem myopathy COL6A3 91 Bifunctional enzyme HSD17B4 92 Biotinidase BTD 93 Björnstad syndrome BCS1L 94 Bloom syndrome BLM 95 Brachytelephalangic chondrodysplasia punctata ARSE 96 Brittle cornea syndrome ZNF Caffey disease COL1A1 98 Canavan disease ASPA 99 Carbamoylphosphate synthetase CPS1

13 Pagina 11 / Cardioencephalomyopathy, fatal infantile, due to cytochrome c SCO2 oxidase Cardioencephalomyopathy, fatal infantile, due to cytochrome c COX15 oxidase Carnitine, systemic primary SLC22A5 103 Carnitine palmitoyl transferase 1A CPT1A 104 Carnitine palmitoyl transferase II, infantile form CPT2 105 Carnitine palmitoyl transferase II, neonatal form CPT2 106 Carnitine-acylcarnitine translocase SLC25A Carpenter syndrome RAB Cartilage-hair hypoplasia RMRP 109 Cataract - intellectual deficit - hypogonadism RAB3GAP2 110 Cataract 40, X-linked NHS 111 Cerebellar ataxia - intellectual deficit - dysequilibrium syndrome VLDLR 112 Cerebral dysgenesis-neuropathyichthyosis-palmoplantar SNAP29 keratoderma syndrome 113 Cerebrotendinous xanthomatosis CYP27A1 114 Charcot-Marie-Tooth disease axonal type 2B LMNA 115 Charcot-Marie-Tooth disease type 4A GDAP1 116 Charcot-Marie-Tooth disease type 4E EGR2 117 Charcot-Marie-Tooth disease type 4F PRX

14 Pagina 12 / Charcot-Marie-Tooth disease type 4H FGD4 119 Charcot-Marie-Tooth disease, type 1A PMP Charcot-Marie-Tooth disease, type 1B MPZ 121 Charcot-Marie-Tooth disease, type 1E PMP Charcot-Marie-Tooth disease, type 2I MPZ 123 Charcot-Marie-Tooth disease, type 2J MPZ 124 Chediak-Higashi syndrome LYST 125 Chilblain lupus SAMHD1 126 Childhood-onset hypophosphatasia ALPL 127 Cholestasis, benign recurrent intrahepatic ATP8B1 128 Cholestasis, benign recurrent intrahepatic, ABCB Cholestasis, intrahepatic, of pregnancy, ATP8B1 130 Cholestasis, intrahepatic, of pregnancy, ABCB4 131 Cholestasis, progressive familial intrahepatic ATP8B1 132 Cholestasis, progressive familial intrahepatic ABCB Cholestasis, progressive familial intrahepatic ABCB4 134 Chondrodysplasia, Blomstrand type PTH1R 135 Citrullinemia type I ASS1 136 Classic congenital adrenal hyperplasia due to 21-hydroxylase CYP21A2

15 Pagina 13 / Classic galactosemia GALT 138 Classic maple syrup urine disease DBT 139 Classical homocystinuria CBS 140 COACH syndrome TMEM Cockayne syndrome type A ERCC8 142 Cockayne syndrome type B ERCC6 143 Coenzyme Q10, primary, COQ9 144 Coffin-Lowry syndrome RPS6KA3 145 COFS syndrome ERCC6 146 Cohen Syndrome type VPS13B 147 Cold-induced sweating syndrome CRLF1 148 Combined immuno with skin granulomas RAG1 149 Combined immuno with skin granulomas RAG2 150 Combined oxidative phosphorylation defect type MRPS Combined oxidative phosphorylation defect type MRPS Combined oxidative phosphorylation TUFM 153 Combined pituitary hormone deficiencies, genetic forms HESX1 154 Combined pituitary hormone deficiencies, genetic forms POU1F1 155 Combined pituitary hormone deficiencies, genetic forms PROP1 156 Combined pituitary hormone with spine LHX3 abnormalities 157 Complete androgen insensitivity syndrome AR 158 Complex I, mitochondrial respiratory chain, of NDUFS6

16 Pagina 14 / Congenital bile acid synthesis defect type 4 glycosylation type 1a glycosylation type 1b glycosylation type 1e glycosylation type 1j glycosylation type 2a glycosylation type 2c glycosylation type 2d glycosylation type 2f glycosylation type Ic glycosylation type Ik glycosylation, type Id glycosylation, type If glycosylation, type Ig glycosylation, type Ih glycosylation, type Ii glycosylation, type IIb glycosylation, type IIe AMACR PMM MPI DPM DPAGT MGAT SLC35C B4GALT SLC35A ALG ALG ALG MPDU ALG ALG ALG MOGS COG7

17 Pagina 15 / glycosylation, type IIg glycosylation, type IIh glycosylation, type Il glycosylation, type Im glycosylation, type In glycosylation, type Iq Congenital fibrinogen (gene FGA) Congenital heart defects, nonsyndromic, 1, X-linked Congenital hereditary endothelial dystrophy type II Congenital lipoid adrenal hyperplasia Congenital malabsorptive diarrhea due to paucity of enteroendocrine cells Congenital muscular dystrophy type 1A Congenital muscular dystrophy type 1D Congenital muscular dystrophy type 4B Congenital muscular dystrophy type 5B Congenital muscular dystrophy with cerebellar involvement Congenital muscular dystrophy with cerebellar involvement COG COG ALG DOLK RFT SRD5A FGA ZIC SLC4A STAR NEUROG LAMA LARGE FKTN FKRP POMGNT POMT1

18 Pagina 16 / Congenital muscular dystrophy with cerebellar involvement POMT2 195 Corneal dystrophy - perceptive deafness SLC4A Corpus callosum agenesis - neuronopathy SLC12A6 197 Corpus callosum hypoplasiaretardation-adducted thumbsspasticity-hydrocephalus L1CAM syndrome 198 Cowden syndrome PTEN 199 Craniofrontonasal dysplasia EFNB1 200 Cutis laxa, autosomal dominant FBLN5 201 Cutis laxa, autosomal recessive, type IA FBLN5 202 Cutis laxa, autosomal recessive, type IB EFEMP2 203 Cutis laxa, autosomal recessive, type IIA ATP6V0A2 204 Cystic fibrosis; mucoviscidosis CFTR 205 Cystinosis CTNS 206 Deafness - encephaloneuropathy - obesity - valvulopathy PDSS1 207 Dejerine-Sottas disease MPZ 208 Dejerine-Sottas disease PMP Dent disease CLCN5 210 Dent disease OCRL 211 Desmosterolosis DHCR Diabetes mellitus, noninsulindependent ABCC8 213 Diabetes mellitus, permanent neonatal ABCC8 214 Diabetes mellitus, transient neonatal ABCC8 215 Diastrophic dwarfism SLC26A2

19 Pagina 17 / Dihydropyrimidine dehydrogenase DPYD 217 Dilated cardiomyopathy with ataxia DNAJC Donnai-Barrow syndrome LRP2 219 Duchenne muscular dystrophy DMD 220 Dyskeratosis congenita X-linked DKC1 221 Dystrophic epidermolysis bullosa pruriginosa COL7A1 222 Early infantile epileptic encephalopathy ARX 223 Early infantile epileptic encephalopathy SLC25A Ectodermal dysplasia 1, hypohidrotic, X-linked EDA 225 Ectodermal dysplasia, hypohidrotic, with immune IKBKG 226 Ectodermal, dysplasia, anhidrotic, lymphedema and IKBKG immuno 227 Ehlers-Danlos syndrome type PLOD1 228 Ehlers-Danlos syndrome, cardiac valvular type COL1A2 229 Ehlers-Danlos syndrome, type I COL1A1 230 Ehlers-Danlos syndrome, type VIIA COL1A1 231 Eiken syndrome PTH1R 232 Ellis-van Creveld syndrome EVC2 233 Ellis-van Creveld syndrome EVC 234 Encephalopathy due to prosaposin PSAP 235 Epidermolysis bullosa simplex with muscular dystrophy PLEC 236 Epidermolysis bullosa simplex with pyloric atresia PLEC

20 Pagina 18 / Epilepsy, progressive myoclonic 2A (Lafora) EPM2A 238 Epilepsy, progressive myoclonic 2B (Lafora) NHLRC1 239 Epilepsy, pyridoxine-dependent ALDH7A1 240 Epileptic encephalopathy, early infantile, ST3GAL3 241 Epileptic encephalopathy, early infantile, CDKL5 242 Epileptic encephalopathy, early infantile, ARHGEF9 243 Epileptic encephalopathy, early infantile, PCDH Escobar syndrome CHRNG 245 Ethylmalonic encephalopathy ETHE1 246 Exudative vitreoretinopathy 2, X- linked NDP 247 Fabry disease GLA 248 Failure of tooth eruption, primary PTH1R 249 Familial dysautonomia IKBKAP 250 Familial hypomagnesemia - hypercalciuria - nephrocalcinosis CLDN19 severe ocular involvement 251 Familial Mediterranean fever MEFV 252 Fanconi anemia complementation group C FANCC 253 Fatal infantile lactic acidosis with methylmalonic aciduria SUCLG1 254 Fatal mitochondrial disease due to combined oxidative TSFM phosphorylation Favism G6PD 256 Fertile eunuch syndrome GNRHR 257 Fetal akinesia deformation sequence RAPSN

21 Pagina 19 / Fetal akinesia deformation sequence DOK7 259 Fetal Gaucher disease GBA 260 FG syndrome CASK 261 Fibular hypoplasia or aplasia - femoral bowing - oligodactyly WNT7A 262 Fraser syndrome (gene FRAS1) FRAS1 263 Fraser syndrome (gene FRAS2) FREM2 264 Free sialic acid storage disease, infantile form SLC17A5 265 French-Canadian type Leigh syndrome LRPPRC 266 Fucosidosis FUCA1 267 Fukuyama congenital muscular dystrophy FKTN 268 Fumaric aciduria FH 269 Galactokinase with cataracts GALK1 270 Gallbladder disease ABCB4 271 Gaucher disease type GBA 272 Gaucher disease type GBA 273 Gaucher disease type 3C GBA 274 Geleophysic dysplasia ADAMTSL2 275 Generalized junctional epidermolysis bullosa, non-herlitz COL17A1 type 276 Glutaric acidemia type 2 (gene ETFA) ETFA 277 Glutaric acidemia type 2 (gene ETFB) ETFB 278 Glutaric acidemia type 2 (gene ETFDH) ETFDH 279 Glutaryl-CoA dehydrogenase GCDH

22 Pagina 20 / Glutathione synthetase with 5-oxoprolinuria GSS 281 Glycine encephalopathy AMT 282 Glycine encephalopathy GCSH 283 Glycine encephalopathy GLDC 284 Glycogen storage disease due to acid maltase GAA 285 Glycogen storage disease due to glucose-6-phosphatase G6PC type 1a 286 Glycogen storage disease due to glucose-6-phosphatase SLC37A4 type b 287 Glycogen storage disease due to glucose-6-phosphatase SLC37A4 type c 288 Glycogen storage disease due to glycogen branching enzyme, childhood combined GBE1 hepatic and myopathic form 289 Glycogen storage disease due to glycogen debranching enzyme AGL 290 Glycogen storage disease due to muscle glycogen phosphorylase PYGM 291 GM1 gangliosidosis type GLB1 292 GM1 gangliosidosis type GLB1 293 GM1 gangliosidosis type GLB1 294 GRACILE syndrome BCS1L 295 Greenberg dysplasia LBR 296 Griscelli disease type MYO5A 297 Griscelli disease type RAB27A 298 Guanidinoacetate methyltransferase GAMT 299 Hemochromatosis, type 2A HFE2

23 Pagina 21 / Hemolytic anemia due to G6PD G6PD 301 Hemolytic anemia due to red cell pyruvate kinase PKLR 302 Hemophagocytic lymphohistiocytosis, familial, PRF1 303 Hemophagocytic lymphohistiocytosis, familial, UNC13D 304 Hemophagocytic lymphohistiocytosis, familial, STX Hemophagocytic lymphohistiocytosis, familial, STXBP2 306 Hemophilia A F8 307 Hemophilia B F9 308 Hepatic venoocclusive disease with immuno SP Hepatoencephalopathy due to combined oxidative GFM1 phosphorylation type Hereditary fructose intolerance ALDOB 311 Hereditary sensory and autonomic neuropathy type NTRK1 312 Hermansky-Pudlak syndrome AP3B1 313 Hermansky-pudlak syndrome PLDN 314 Heterotaxy, visceral, 1, X-linked ZIC3 315 Histidinemia HAMP 316 Holocarboxylase synthetase HLCS 317 Hoyeraal-Hreidarsson syndrome DKC1 318 Hyaline fibromatosis syndrome ANTXR2 319 Hyperammonemia due to N- acetylglutamate synthetase NAGS 320 Hyper-IgE recurrent infection syndrome, autosomal recessive DOCK8

24 Pagina 22 / Hyperinsulinemic hypoglycemia, familial, ABCC8 322 Hyperornithinemiahyperammonemiahomocitrullinuria SLC25A Hypoglycemia of infancy, leucinesensitive ABCC8 324 Hypogonadotropic hypogonadism 7 without anosmia GNRHR 325 Hypomyelination - congenital cataract FAM126A 326 Hypoparathyroidism - intellectual deficit - dysmorphism syndrome TBCE 327 Hypophosphatemic rickets CLCN5 328 Ichthyosis follicularis - alopecia - photophobia MBTPS2 329 Ichthyosis, autosomal recessive 4B (harlequin) ABCA Ichthyosis, congenital, autosomal recessive TGM1 331 Ichthyosis, congenital, autosomal recessive 4A ABCA Ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis CLDN1 333 Immuno STIM1 334 Immuno 17, CD3 gamma deficient CD3G 335 Immuno 18, SCID variant CD3E 336 Immuno CD3D 337 Immuno 27A, mycobacteriosis, AR IFNGR1 338 Immuno 28, mycobacteriosis IFNGR2 339 Immuno 29, mycobacteriosis IL12B

25 Pagina 23 / Immuno IL12RB1 341 Immuno 31A, mycobacteriosis, autosomal STAT1 dominant 342 Immuno 31B, mycobacterial and viral infections, STAT1 autosomal recessive 343 Immuno 31C, autosomal dominant STAT1 344 Immuno IKBKG 345 Immuno TYK2 346 Immuno ORAI1 347 Immuno, common variable, ICOS 348 Immuno, common variable, CD Immuno-centromeric instability-facial anomalies DNMT3B syndrome Immunodysregulation, polyendocrinopathy, and FOXP3 enteropathy, X-linked 351 Incontinentia pigmenti, type II IKBKG 352 Infantile bilateral striatal necrosis NUP Infantile hypophosphatasia ALPL 354 Infantile neuroaxonal dystrophy 2A PLA2G6 355 Infantile neuroaxonal dystrophy 2B PLA2G6 356 Infantile onset spinocerebellar ataxia C10orf2 357 Interleukin 1 receptor antagonist IL1RN 358 Isolated CoQ-cytochrome C reductase BCS1L

26 Pagina 24 / Isolated growth hormone type III BTK 360 Isolated thyroid-stimulating hormone TSHB 361 Isovaleric acidemia IVD 362 Jeune syndrome IFT Johanson-Blizzard syndrome UBR1 364 Joubert syndrome NPHP1 365 Joubert syndrome TMEM Joubert syndrome with hepatic defect RPGRIP1L 367 Joubert syndrome with ocular defect AHI1 368 Joubert syndrome with oculorenal defect CEP Junctional epidermolysis bullosa - pyloric atresia ITGA6 370 Junctional epidermolysis bullosa with piloric atresia ITGB4 371 Junctional epidermolysis bullosa, Herlitz type (gene LAMA3) LAMA3 372 Junctional epidermolysis bullosa, Herlitz type (gene LAMB3) LAMA3 373 Junctional epidermolysis bullosa, Herlitz type (gene LAMC2) LAMC2 374 Junctional epidermolysis bullosa, non-herlitz type ITGB4 375 Junctional epidermolysis bullosa, non-herlitz type (gene LAMA3) LAMA3 376 Junctional epidermolysis bullosa, non-herlitz type (gene LAMB3) LAMB3 377 Junctional epidermolysis bullosa, non-herlitz type (gene LAMC2) LAMC2 378 Juvenile neuronal ceroid lipofuscinosis CLN3 379 Kahrizi syndrome SRD5A3

27 Pagina 25 / Kelley-Seegmiller syndrome HPRT1 381 Kennedy disease AR 382 Ketoacidosis due to betaketothiolase ACAT1 383 Krabbe disease GALC 384 Krabbe disease PSAP 385 Lacticacidemia due to PDX PDHX 386 Late infantile neuronal ceroid lipofuscinosis MFSD8 387 Late infantile neuronal ceroid lipofuscinosis CLN5 388 Late infantile neuronal ceroid lipofuscinosis CLN6 389 Late infantile neuronal ceroid lipofuscinosis CLN8 390 Lathosterolosis SC5DL 391 Leigh syndrome BCS1L 392 Leigh syndrome DLD 393 Leigh syndrome NDUFAF2 394 Leigh syndrome NDUFS4 395 Leigh syndrome NDUFS7 396 Leigh syndrome due to cytochrome c oxidase COX Leigh syndrome due to mitochondrial complex I NDUFS3 398 Leigh syndrome due to mitochondrial complex I NDUFS8 399 Leigh syndrome due to mitochondrial COX COX Leigh syndrome with nephrotic syndrome COQ2 401 Leigh syndrome with nephrotic syndrome PDSS2

28 Pagina 26 / Leigh syndrome, due to COX SURF1 403 Leigh syndrome, X-linked PDHA1 404 Leprechaunism INSR 405 Lesch-Nyhan syndrome HPRT1 406 Lethal acantholytic epidermolysis bullosa DSP 407 Lethal ataxia with deafness and optic atrophy PRPS1 408 Lethal congenital contractural syndrome ERBB3 409 Lethal congenital contracture syndrome type GLE1 410 Lethal osteosclerotic bone dysplasia FAM20C 411 Lethal restrictive dermopathy LMNA 412 Lethal restrictive dermopathy ZMPSTE Leukocyte adhesion, type III FERMT3 414 Leydig cell adenoma, somatic, with precocious puberty LHCGR 415 Leydig cell hypoplasia with hypergonadotropic hypogonadism LHCGR 416 Leydig cell hypoplasia with pseudohermaphroditism LHCGR 417 Lhermitte-Duclos syndrome PTEN 418 Limb girdle dystrophy with epidermolysis bullosa simplex PLEC 419 Lissencephaly TUBA1A 420 Lissencephaly syndrome, Norman-Roberts type RELN 421 Lissencephaly, X-linked DCX 422 Long chain 3-hydroxyacyl-CoA dehydrogenase HADH 423 Luteinizing hormone resistance, female LHCGR

29 Pagina 27 / Lymphoproliferative syndrome, X- linked, XIAP 425 Macrocephaly/autism syndrome PTEN 426 Macroglobulinemia, Waldenstrom MYD Macular degeneration, age-related, FBLN5 428 Mandibuloacral dysplasia with type A lipodystrophy LMNA 429 Mandibuloacral dysplasia with type B lipodystrophy ZMPSTE Mannosidosis, alpha-, types I and II MAN2B1 431 Maple syrup urine disease DLD 432 Maple syrup urine disease (gene BCKDHA) BCKDHA 433 Maple syrup urine disease (gene BCKDHB) BCKDHB 434 Marinesco-Sjögren syndrome SIL1 435 Masa syndrome L1CAM 436 Meckel syndrome type MKS1 437 Meckel syndrome, type RPGRIP1L 438 Medium chain acyl-coa dehydrogenase ACADM 439 Megalencephalic leukoencephalopathy with MLC1 subcortical cysts 440 Menkes disease ATP7A 441 Mental retardation and microcephaly with pontine and CASK cerebellar hypoplasia 442 Mental retardation, autosomal recessive PRSS Mental retardation, autosomal recessive ST3GAL3 444 Mental retardation, autosomal recessive TRAPPC9

30 Pagina 28 / Mental retardation, autosomal recessive NSUN2 446 Mental retardation, autosomal recessive, GRIK2 447 Mental retardation, with or without nystagmus CASK 448 Mental retardation, X-linked NLGN4X 449 Mental retardation, X-linked RPS6KA3 450 Mental retardation, X-linked 21/ IL1RAPL1 451 Mental retardation, X-linked 30/ PAK3 452 Mental retardation, X-linked GDI1 453 Mental retardation, X-linked ARHGEF6 454 Mental retardation, X-linked ACSL4 455 Mental retardation, X-linked RAB39B 456 Mental retardation, X-linked FTSJ1 457 Mental retardation, X-linked DLG3 458 Mental retardation, X-linked BRWD3 459 Mental retardation, X-linked SYP 460 Mental retardation, X-linked ZNF Mental retardation, X-linked syndromic FGD1 462 Mental retardation, X-linked syndromic AP1S2 463 Mental retardation, X-linked syndromic, Christianson type SLC9A6 464 Mental retardation, X-linked syndromic, Nascimento-type UBE2A 465 Mental retardation, X-linked syndromic, Raymond type ZDHHC9 466 Mental retardation, X-linked syndromic, Turner type HUWE1 467 Mental retardation, X-linked, FRAXE type AFF2 468 Mental retardation, X-linked, Snyder-Robinson type SMS

31 Pagina 29 / Mental retardation, X-linked, syndromic UPF3B 470 Mental retardation, X-linked, syndromic 15 (Cabezas type) CUL4B 471 Mental retardation, X-linked, syndromic, Claes-Jensen type KDM5C 472 Mental retardation, X-linked, with cerebellar hypoplasia and OPHN1 distinctive facial appearance 473 Mental retardation, X-linked, with isolated growth hormone SOX3 474 Mental retardation-hypotonic facies syndrome, X-linked ATRX 475 Metachromatic leukodystrophy ARSA 476 Metachromatic leukodystrophy PSAP 477 Metaphyseal chondrodysplasia, Murk Jansen type PTH1R 478 Metaphyseal dysplasia without hypotrichosis RMRP 479 Methylmalonic acidemia with homocystinuria, type cblc MMACHC 480 Methylmalonic acidemia with homocystinuria, type cbld MMACHC 481 Mevalonic aciduria MVK 482 Micro syndrome RAB3GAP1 483 Microphthalmia, syndromic BCOR 484 Mitochondrial complex I NDUFA1 485 Mitochondrial complex I NDUFAF2 486 Mitochondrial complex I NDUFAF4 487 Mitochondrial complex I NDUFS3

32 Pagina 30 / Mitochondrial complex I Mitochondrial complex I Mitochondrial complex IV Mitochondrial complex IV Mitochondrial complex IV Mitochondrial complex IV Mitochondrial DNA depletion syndrome 1 (MNGIE type) Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) Mitochondrial DNA depletion syndrome 8B (MNGIE type) Mitochondrial DNA depletion syndrome, hepatocerebral form due to DGUOK 3 Mitochondrial DNA depletion syndrome, myopathic form Mitochondrial neurogastrointestinal encephalomyopathy Mitochondrial respiratory chain complex III Mitochondrial respiratory chain complex III NDUFS NDUFV COX COX6B FASTKD2 SCO TYMP SUCLA RRM2B RRM2B DGUOK TK POLG UQCRB UQCRQ

33 Pagina 31 / Mitochondrial trifunctional protein HADHA 504 Mitochondrial trifunctional protein HADHB 505 Mohr-Tranebjaerg syndrome TIMM8A 506 Mowat-Wilson syndrome ZEB2 507 Mucolipidosis type GNPTAB 508 Mucolipidosis type GNPTAB 509 Mucolipidosis type MCOLN1 510 Mucopolysaccharidosis Ih IDUA 511 Mucopolysaccharidosis Ih/s IDUA 512 Mucopolysaccharidosis Is IDUA 513 Mucopolysaccharidosis type IDS 514 Mucopolysaccharidosis type 3A (Sanfilippo syndrome type A) SGSH 515 Mucopolysaccharidosis type 4B GLB1 516 Mucopolysaccharidosis type ARSB 517 Mucopolysaccharidosis type GUSB 518 Mucopolysaccharidosis type IIIB (Sanfilippo B) NAGLU 519 MULIBREY nanism TRIM Multiple epiphyseal dysplasia type SLC26A2 521 Multiple pterygium syndrome, lethal type CHRNA1 522 Multiple pterygium syndrome, lethal type CHRND 523 Multiple pterygium syndrome, lethal type CHRNG 524 Muscle-eye-brain disease FKRP 525 Muscle-eye-brain disease LARGE 526 Myasthenia gravis, neonatal transient CHRNG 527 Myasthenia, limb-girdle, familial DOK7

34 Pagina 32 / Myasthenic syndrome, fastchannel congenital CHRNA1 529 Myasthenic syndrome, fastchannel congenital CHRND 530 Myasthenic syndrome, slowchannel congenital CHRNA1 531 Myasthenic syndrome, slowchannel congenital CHRND 532 Myopathy, tubular aggregate, STIM1 533 Myopathy, tubular aggregate, ORAI1 534 Nance-Horan syndrome NHS 535 Navajo neurohepatopathy MPV Nemaline myopathy NEB 537 Neonatal adrenoleukodystrophy (gene PEX12) PEX Neonatal adrenoleukodystrophy (gene PEX26) PEX Neonatal adrenoleukodystrophy (gene PEX5) PEX5 540 Nephrolithiasis, type I CLCN5 541 Nephronophthisis 2, infantile INVS 542 Nephrotic syndrome, tupe PLCE1 543 Nephrotic syndrome, type NPHS1 544 Nephrotic syndrome, type NPHS2 545 Nephrotic syndrome, type 5, with or without ocular abnormalities LAMB2 546 Neurodegeneration due to 3- hydroxyisobutyryl-coa hydrolase HIBCH 547 Neurodegeneration due to cerebral folate transport FOLR1 548 Neuronal ceroid lipofuscinosis TPP1 549 Neuropathy, congenital hypomyelinating MPZ

35 Pagina 33 / Neutropenia, severe congenital 3, autosomal recessive HAX1 551 Niemann-Pick disease type A SMPD1 552 Niemann-Pick disease type B SMPD1 553 Niemann-Pick disease type C NPC1 554 Niemann-Pick disease type C NPC2 555 Nijmegen breakage syndrome NBN 556 Norrie disease NDP 557 ntal retardation, autosomal recessive TUSC3 558 Occipital horn syndrome ATP7A 559 Oculocerebrorenal syndrome OCRL 560 Omenn syndrome DCLRE1C 561 Omenn syndrome (gene RAG1) RAG1 562 Omenn syndrome (gene RAG2) RAG2 563 Opitz GBBB syndrome, type I MID1 564 Ornithine transcarbamylase OTC 565 Osteogenesis imperfecta type LEPRE1 566 Osteogenesis imperfecta type VII CRTAP 567 Osteogenesis imperfecta, type I COL1A1 568 Osteogenesis imperfecta, type II COL1A1 569 Osteogenesis imperfecta, type III COL1A1 570 Osteogenesis imperfecta, type IV COL1A1 571 Osteopetrosis with renal tubular acidosis CA2 572 Osteopetrosis, autosomal recessive OSTM1 573 Paget disease, juvenile TNFRSF11B 574 Panhypopituitarism, X-linked SOX3 575 Pantothenate kinase-associated neurodegeneration PANK2 576 Partial androgen insensitivity syndrome AR

36 Pagina 34 / Pelizaeus-Merzbacher-like due to GJC2 mutation GJC2 578 Peroxisomal acyl-coa oxidase ACOX1 579 Peroxisome biogenesis disorder 11A (Zellweger) PEX Peroxisome biogenesis disorder 11B PEX Peroxisome biogenesis disorder 6A (Zellweger) PEX Peroxisome biogenesis disorder 6B PEX Perrault syndrome HSD17B4 584 Phenylketonuria PAH 585 Pierson syndrome LAMB2 586 Pitt-Hopkins syndrome TCF4 587 Plasminogen type PLG 588 Pontocerebellar hypoplasia type 2A TSEN Pontocerebellar hypoplasia type TSEN Porphyria, congenital erythropoietic UROS 591 Precocious puberty, male LHCGR 592 Primary lateral sclerosis, juvenile ALS2 593 Progressive epilepsy - intellectual deficit, Finnish type CLN8 594 Properdin, X-linked CFP 595 Propionic acidemia (gene PCCA) PCCA 596 Propionic acidemia (gene PCCB) PCCB 597 Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis CLCN5 598 Proximal spinal muscular atrophy type SMN1 599 Proximal spinal muscular atrophy type SMN1

37 Pagina 35 / Proximal spinal muscular atrophy type SMN1 601 Proximal spinal muscular atrophy type SMN1 602 Pseudohermaphroditism, male, with gynecomastia HSD17B3 603 Pseudohypoaldosteronism type 1, autosomal recessive (gene SCNN1A SCNN1A) 604 Pseudohypoaldosteronism type 1, autosomal recessive (gene SCNN1B SCNN1B) 605 Pseudohypoaldosteronism type 1, autosomal recessive (gene SCNN1G SCNN1G) 606 Pseudovaginal perineoscrotal hypospadias SRD5A2 607 Pycnodysostosis CTSK 608 Pyogenic bacterial infections, recurrent, due to MYD MYD Pyridoxal phosphate-responsive seizures PNPO 610 Pyruvate carboxylase PC 611 Pyruvate dehydrogenase phosphatase PDP1 612 Renal-hepatic-pancreatic dysplasia NPHP3 613 Renpenning syndrome PQBP1 614 Rett syndrome, congenital variant FOXG1 615 Rhizomelic chondrodysplasia punctata type PEX7 616 Rhizomelic chondrodysplasia punctata type AGPS 617 Rigid spine syndrome SEPN1 618 Roberts syndrome ESCO2

38 Pagina 36 / Roussy-Levy syndrome MPZ 620 Roussy-Levy syndrome PMP Sandhoff disease HEXB 622 Sanfilippo syndrome type C HGSNAT 623 Schneckenbecken dysplasia SLC35D1 624 Schwartz-Jampel syndrome HSPG2 625 Seckel syndrome ATR 626 Senior-Loken syndrome CEP Senior-Loken syndrome NPHP4 628 Senior-Loken syndrome NPHP3 629 Senior-Loken syndrome IQCB Sensory ataxic neuropathy - dysarthria - ophthalmoparesis Severe combined immuno due to adenosine deaminase Severe combined immuno due to complete RAG1/2 Severe combined immuno due to complete RAG1/2 Severe combined immuno due to DCLRE1C Severe combined immuno with microcephaly, growth retardation, and sensitivity to ionizing radiation Severe combined immuno with sensitivity to ionizing radiation Severe generalized recessive dystrophic epidermolysis bullosa POLG ADA RAG RAG DCLRE1C NHEJ LIG COL7A1

39 Pagina 37 / Severe neonatal-onset encephalopathy with MECP2 microcephaly 639 Severe T-cell immuno - congenital alopecia - nail FOXN1 dystrophy 640 Short-rib thoracic dysplasia 3 with or without polydactyly DYNC2H1 641 Shwachman-Diamond syndrome SBDS 642 Sialidosis, type I NEU1 643 Sialidosis, type II NEU1 644 Sickle cell anemia HBB 645 Simpson-Golabi-Behmel syndrome type OFD1 646 Simpson-Golabi-Behmel syndrome, type GPC3 647 Síndrome de Dursun G6PC3 648 Sjogren-Larsson syndrome ALDH3A2 649 Smith-Lemli-Opitz syndrome DHCR7 650 Sotos syndrome NSD1 651 Spastic paralysis, infantile onset ascending ALS2 652 Spastic paraplegia type 2, X-linked PLP1 653 Spinal muscular atrophy with respiratory distress IGHMBP2 654 Stocco dos Santos X-linked mental retardation syndrome SHROOM4 655 Stormorken syndrome STIM1 656 Stüve-Wiedemann syndrome LIFR 657 Subcortical laminal heteropia, X- linked DCX 658 Succinyl CoA:3-oxoacid CoA transferase OXCT1 659 Sudden infant death with dysgenesis of the testes syndrome TSPYL1

40 Pagina 38 / Sulfite oxidase due to molybdenum cofactor MOCS1 type A (gene MOCS1) 661 Sulfite oxidase due to molybdenum cofactor MOCS2 type A (gene MOCS2) 662 Sulfocysteinuria SUOX 663 Surfactant metabolism dysfunction, pulmonary, SFTPB 664 Surfactant metabolism dysfunction, pulmonary, SFTPC 665 Surfactant metabolism dysfunction, pulmonary, ABCA3 666 Syndromic microphthalmia type STRA6 667 Tay-Sachs disease HEXA 668 T-B+ severe combined immuno due to gamma IL2RG chain 669 T-B+ severe combined immuno due to JAK JAK3 670 T-B+ severe combined immuno, X-linked IL2RG 671 Tetra-amelia, autosomal recessive WNT3 672 Thrombocythemia MPL 673 Thrombocytopenia, congenital amegakaryocytic MPL 674 Thrombotic thrombocytopenic purpura, familial ADAMTS Tooth agenesis, selective, X- linked EDA 676 Trichothiodystrophy, complementation group A GTF2H5 677 Tyrosinemia type FAH 678 Tyrosinemia type TAT 679 Tyrosinemia type HPD

41 Pagina 39 / Ullrich congenital muscular dystrophy COL6A1 681 Ullrich congenital muscular dystrophy COL6A2 682 Ullrich congenital muscular dystrophy COL6A3 683 Unverricht-Lundborg disease CSTB 684 Usher syndrome type MYO7A 685 Usher syndrome type 1C USH1C 686 Usher syndrome type 1G USH1G 687 Usher syndrome type 2A USH2A 688 Usher syndrome type 2C GPR Usher syndrome type 3A CLRN1 690 Very long chain acyl-coa dehydrogenase ACADVL 691 Vitamin B12-responsive methylmalonic acidemia type cbla MMAA 692 Vitamin B12-responsive methylmalonic acidemia type cblb MMAB 693 Vitamin B12-unresponsive methylmalonic acidemia type mut MUT 694 Vitamin D-dependent rickets type 2A VDR 695 Vitamin D-dependent rickets, type I CYP27B1 696 Waardenburg-Shah syndrome 4A EDNRB 697 Waardenburg-Shah syndrome 4B EDN3 698 Walker-Warburg syndrome (gene POMGNT1) POMGNT1 699 Walker-Warburg syndrome (gene POMT1) POMT1 700 Walker-Warburg syndrome (gene POMT2) POMT2 701 Weyers acrodental dysostosis EVC 702 Wilson disease ATP7B

42 Pagina 40 / Wiskott-Aldrich syndrome WAS 704 Wolcott-Rallison syndrome EIF2AK3 705 Wrinkly skin syndrome ATP6V0A2 706 Xeroderma pigmentosum complementation group A XPA 707 Xeroderma pigmentosum complementation group E DDB2 708 Xeroderma pigmentosum, group C XPC 709 Xeroderma pigmentosum/cockayne syndrome complex ERCC3 complementation group B 710 Xeroderma pigmentosum/cockayne syndrome complex ERCC2 complementation group D 711 Xeroderma pigmentosum/cockayne syndrome complex ERCC4 complementation group F 712 Xeroderma pigmentosum/cockayne syndrome complex ERCC5 complementation group G 713 X-linked agammaglobulinemia BTK 714 X-linked centronuclear myopathy MTM1 715 X-linked Charcot-Marie-Tooth disease type PRPS1 716 X-linked creatine transporter SLC6A8 717 X-linked distal spinal muscular atrophy ATP7A 718 X-linked hyper-igm syndrome CD40LG 719 X-linked intellectual deficit with marfanoid habitus MED12

43 Pagina 41 / X-linked lymphoproliferative disease SH2D1A 721 X-linked severe congenital neutropenia WNT10A 722 X-linked spinal muscular atrophy type UBA1 723 Zellweger syndrome 1A PEX1 724 Zellweger syndrome 7A PEX26 Roma, 23/10/2015 Il Genetista Il Direttore Dr.ssa Marina Baldi Dr. F. Fiorentino