Up to Now 216 Different Autosomal Recessive Diseases in Which the Responsible Mutation(S)

The Molecular basis of Autosomal Recessive Diseases among the Arabs and Druze in Israel (goldenhelix.org/server/Israeli)

1. The Molecular basis of Autosomal Recessive Diseases among the Muslim Arabs (in italics diseases found among Muslim Bedouins only)

Single Mutation Abetalipoproteinemia MTP gene deletion Acrodermatitis enteropathica SLC39A4 p.A483X Afibrinogenemia congenital FGB p.W467X Aicardi Goutieres syndrome SAMHD1 p.120_123 del Allgrove syndrome (Triple A) AAAS p.Q15K Alopecia neurological defect and endocrinopathy syndrome RBM28 c.T1052C Alstrom syndrome ALMS1 C2726fs Arthrogryposis autosomal recessive SYNE 1 A>G acceptor site 136/137 Arthrogryposis renal dysfunction and cholestasis (ARC) VPS33B c.403+1G>A Aspartylglucosaminuria AGA p.S72P Ataxia with oculomotor apraxia APTX p.W279X Bartter syndrome, infantile variant with sensorineuronal deafness BSND p.G28A Brachydactyly type A2 BMPR1B p.G377A Brittle cornea syndrome ZFF469 c. 9527 delG Calcinosis, tumoral with hyperphosphatasemia. GALNT3 c.1524G+1 >A Cardiomyopathy dilated, neonatal isolated SDHA p. G555E Carnitine Palmitoyl transferase deficiency CPTII p.R503C Carnitine-acylcarnitine translocase deficiency CACT p.Q238R Cataracts, autosomal recessive GCNT2 p.W328X CEDNIK SANP29 c.220delG Ceroid lipofuscinosis, 8 CLN8 Q256E Cleft lip/palate ectodermal dysplasia, CLPED1 CLPED1 p.323_1bpdel Color blindness total (achromatopsia) CNGA3 p.V529M Complement C7 deficiency C7 p.G1135C Complex III deficiency, mitochondrial respiratory chain UQCRQ c.208C → T Congenital absence of alpha fetoprotein AFP p.T294fs25X Congenital analbuminemia HAS c.228_229delAT 2

Congenital chloride diarrhea SLV26A3 p.G187X Congenital disorder of glycosylation IIc SLC35C1 Thr308Arg Congenital thyroid hormone and glucocorticoid deficiency TSHR p.C2024T Cutis laxa autosomal recessive, type II ATP6V0A2 c.2375C>G Cutis laxa autosomal recessive PYCR1 c.617_633+6del Cystinuria SLC3A1 c.891+4A>G Enhanced S-cone syndrome NR2E3 c.119-2A>C Factor XI deficiency (PTA) FXI p.E117X Factor XIII deficiency F13A1 p.L660P Familal hypocalciuric hypercalcemia CASR Q459R Familial erythrophagocytosis FHL3 c.1755insT Fanconi anemia G FANCG 212T>C Fanconi syndrome with hypophosphatemic rickets SLC34A1 2061_2081dup Fran-Ter Haar syndrome SH3PXD2B c.76-2A>C Glucose-galactose malabsorption SLC5A1 p.C255W Glycogen storage disease type 1a G6PC p.V66G Growth Hormone Deficiency Type Ib GHRH-R p.R357C H syndrome SLC29A3 c.1279G>A Hemolytic uremic syndrome, Complement H factor 1 deficiency CFH 24bpdel (ex20) Hereditary haemorrhagic telangiectasia ENG c.932T>G Hereditary spastic paraplegia type 11 SPG11 Q40X Hereditary spastic paraplegia type 15 SPG15 c.6702_6771 Hermansky-Pudlak syndrome HPS6 c.1066-1067insG Hypocalciuric hypercalcemia CASR Q459R Hypophosphatasia, infantile ALPL p.R433C Hypotonia - cystinuria syndrome SLC3A1, Deletion Hypotrichosis simplex LIPH c.280_369dup Ichthyosis Congenita ABCA12 Ex6_del Ichthyosis with hypotrichosis ST14 p.G827R Inclusion Body Myopathy GNE p.M712T Infantile bilateral striatal necrosis NUP62 p.Q391P Isolated growth hormone deficiency GH p.R357C Isovarelic academia IVD c.774C>G Johnson Blizzard syndrome UBR1 2598delA Krabbe disease GALC p.D528N Lafora disease EPM2A eEx2-56Kbdel Lethal contractural syndrome type 2 ERBB3 IVS-8A>G Lethal contractural syndrome type 3 PIP5KIC c.G757A Leukocyte adhesion deficiency, type II FUCT1 p.T308R Leukodystrophy with spastic paraparesis dystonia FAH2 c.786+1G>A Limb girdle muscular dystrophy LGMD2B DYSF 23bp_ins Limb girdle muscular dystrophy LGMD2C SGCG p.525del Limb girdle muscular dystrophy LGMD2I FKRP p.R54W Lipoid proteinosis ECM Ex8 splice MACS Syndrome RIN2 c.1731 delC Mal de Meleda (MDM) SLURP-1 p.G86R Mental retardation with progressive microcephaly TRAPPC9 p.R475X Mental retardation, non syndromic CC2D1A p.G408fsX437 Microphthalmia/anophthalmia CHX10 p.A227T 3

Mitochondrial disease due to a defective mitochondrial translation MRPS16 p.A111X Mitochondrial encephalopathy KIAA0971 c.1246C>T Mitochondrial Hsp60 Chaperonopathy disease HSPD1 D29G Myoglobinuria, acute recurrent LPIN1 c.643G>T Neonatal myoclonic epilepsy SLC25A22 p.P206L Nephrotic syndrome steroid resistant NPHS2 p.R138X Neuropathy and bilateral strial necrosis SLC25A19 c.373G>A Nonbullous congenital ichthyosiform erythroderma ALOX12B p.Lys542ArgfsX OSMED COL11A2 p.R845X Osmodysplasia GPC6 deletion Peroxisome Biogenesis disorders PEX2 p.W223X PNPO deficiency PNPO c.284G>A Polymalformative syndrome due to FTO mutation FTO c.947G>A Pontocerebellar hypoplasia type II TSEN54 A370S POR deficiency POR G539R Primary ciliary dyskinesia RSPH9 c.801_803delGAA Progressive familial intrahepatic cholestasis ABCB11 R470Q Progressive Myoclonic epilepsy Unverrich-Lundborg CSTB Expansion Progressive myoclonic epilepsy-ataxia PRICKLE1 R104Q Pseudorheumatoid arthropathy of childhood WISP3 p.C52X Pycnodysostosis CTSK p.K330W Raine syndrome FAM20C c.1672C>T Recurrent rhabdomyolysis LPIN1 c.643G>T Renal glucosuria SLC5A2 p.K321R Reticulosis, familial hystiocytic FHL3 c.1755insT Rickets, 1,25 dehydroxyvitamin D3 resistant VDR p.Y292X Sanfilippo B disease (MPSIIIB) NA-GLU p.R674H SERKAL syndrome WNT4 c.C341T Sialic acid storage disease SLC17A5 c.983G>A Sickle cell anemia HBB G6V Sjogren-Larsson syndrome ALDH3A2 c.682C>T Spinal muscular atrophy type I (SMA1) SMN1 deletion Smith Lemli Opitz DHCR7 p.N52S Spastic paraplegia with thin corpus callosum SPG11 p.Q40X Spondylocostal dysostosis DLL3 p.S198ins5 Spondylo-epi-metaphyseal dysplasia (SEMD) MATN3 c.973T>A Spondylo-meta epiphyseal dysplasia (SMED) DDR2 c.2254 C>T Steroid 5 alpha reductase deficiency SRD5A2 Y235F Stuve-Wiedmann syndrome LIFR 2472-2476del TATGT Thiamine responsive megaloblastic anemia SLC19A2 p.del242fs/259X Trifunctional protein deficieny HADHA c.703C>T Ventricular tachycardia, polymorphic catecholaminergic CASQ 2 p.D307H Weissenbacher-Zweymuller syndrome COL11A2 p.R854X Wilson disease ATP7B c.1639delC Xanthinuria MOCOS p.A776C 4

2 mutations in one gene 3-Hydroxy-3-Methyl Glutaric aciduria HMGCL p.C174Y, p.D42G Acute infantile liver failure TRMU c.500-510del, V279M Ataxia telangiectasia ATM c.497del17514bp, c.7240delA Biotinidase deficiency BTD p.A393C,del p.G34S Ceroid lipofuscinosis, 2 CLN2 c.775delC, E72X Diabetes insipidus, nephrogenic AQP2 p.G298T, p.G542X Ectodermal dysplasia, skin fragility PKP1 c.203-1G>A, c.847-2A>G Epidermolysis bullosa, pyloric atresia and aplasia cutis ITGB4 2279bp deletion, c.delEx27G Hurler syndrome IDU Ex2C>A, Ex8 A>C c.155-156del, c.207- Hypoparathyroidism, mental retardation and dysmorphism TBCE 208delTA Monilethrix TRKHB6 p.E410D, p.G413L Nephronophthisis infantile INVS p.R907X, c.C2719T Osteopetrosis TCIRG1 c.C5233T, c.G4640T Pituitary hormone deficiency (combined) POU1F1 p.F262L, p.W193X Polymicrogyria, bilateral frontal GPR56 IVS9+3G>C, p.C346S Prolidase deficiency PEPD p.S202F, A212P splice junction before exon 4, Renal tubular acidosis with progressive sensorineural deafness ATP6V1B1 340C>T Resitance to thyrotropin TSHR L653V, P68S Rickets, hereditary hypophospatemic ENPP1 c.2248_2249insA, Y901S SMARD1 11delA, L236X Spinal muscular atrophy with respiratory distress Tyrosinemia type II TAT c.1224G>T, R417X Wolman disease LIPA p.S106X, G87V 5

More than 2 mutations in one gene.

Atrichia, with papular lesions HR c.1256delC c.2147delC c.3434delC p.D1012N p.V1056M Citrullinemia type II, neonatal onset SLC25A13 E192K L598R p.532fs Congenital amegakaryotic thrombocytopenia c-MLP c.212+5G>A C127T C76T Congenital insensivity to pain with anhidrosis NTRK1 c.1926insT c.196T p.C1250T p.P689L Combined pituitary hormone deficiencies POU1F1 F262L K230E W193X Congenital lipoid adrenal hyperplasia STAR p.A632G p.G671T p.R193X p.T593del Dyserythropoietic anemia type I (congenital) CDAN1 IVS-12+5G>A p.V867M 3238C>T p.R1040W Epidermolysis bullosa generalized atrophic benign COL17A1 c.2226insTGGA c.3766+1G>A c.4144del4 c.6339delG c.682+1G>A c.737insA IVS51+1G>A p.R1226X p.W796X Factor VII deficiency F7 IVSII+1G>C p.T359M G180R Fanconi Anemia A FANCA deletion IVS42A A>C p.V2291I Gaucher disease GLC D409H p.R48W N370S Glaucoma, congenital CYP1B1 p.G61E p.R469W c.3987G>A 6

Glutaric academia type I GCDH c.1173delG p.A293T p.A392S p.G390R p.L283P p.S305L p.T416I Glutaric academia type II ETHFDH c.1074 G>C c.1425 C>A c.299 T>A Glycogen storage disease type 1b G6PT c.1211delCT p.G149E p.W393X c.G252A GM1 Gangliosidosis GLB1 c.485delT p.H276P p.K346N p.R201H c.Ex16,19bpdel/IVS1 Homocystinuria CBS 7,5bpdel p.I278T p.K102Q/Ex5del p.T262R Hypomagnesemia, primary congenital TRPM6 c.1010+5G>C c.3209-68A>G c.2009+1G>A Hypothyroidism, congenital TPO p.A540X p.G493S p.R540X p.S292F ACADM 362C>T Medium chain acyl CoA dehydrogenase deficiency IVS3-1G>C del621 agta Metachromatic leukodystrophy, late infantile ARSA c.499+1G>A p.C69G p.G14D p.G86D p.Q190H p.S96L Methyl malonic aciduria MUT IVS+3A>G p.A499T p.E414X p.N219Y Molybdenum cofactor deficiency MOCS1 c.722Tdel p.R47L p.R91W 7

Mucolipidosis II/III GNPTAB c.2916insT c.3434+1G>A c.3502_4deltTC IVS 18+1 G>A IVS-2A>G c.500insC p.G106S c.500insC p.G106S Nephrotic syndrome congenital, Finnish type NPHS1 c.2160insC p.C1138T p.C1707G p.E192N p.Glu178X Neuroaxonal dystrophy, infantile PLA2G6 p.G347A p.P223Q p.V691del Niemann Pick type C NPC1 c.2279_81delTCT c.3347delTC del1760F p.A927V p.G992W p.N1156S P691L R1186H p.R404Q Niemann-Pick type A,B disease SMPD1 c.561delT c.677delT C582W F565L G240R W144R Oxalosis I (Primary hyperoxaluria type I) AGTX Ex2splice p.G243A p.G949C Pendred syndrome SLC26A4 p.F667C c.1421delT c.1565delG Pompe disease GAA L299P p.R854X P136L C341insT p.D404N SLC34A3 c.1058G>T Rickets, hereditary hypophospatemic with hypercalciuria c.1238C>A c.846G>A c.905delC c.228delC Sanfilippo A disease ( (MPSIIIA) SGSH p.L411F p.T139M p.Y89X 8

Tay Sachs disease HEXA c.78G>A IVS12 + 2T>C p.T26X Thrombastenia of Glanzmann ITGA2B A97C del 13bp IVS4-3

Mutations in more than one gene Bartter and Gitelman syndrome CLCNKB p.R438H KCNJ11 G220S T71M Bardet Biedl syndrome BBS2 p.V75G BBS3 p.R122X BBS4 p.R295P BBS7 c.E596K BBS11 c.C388T Chronic granulomatous disease NCF2 196 C>T C304T CYBA G70A Congenital neutropenia ELA2 T156C G6PC3 c.785G>A Cone-rod dystrophy ADAM9 c.411-8A>G ABCA4 c.4254-15del23 ABCA4 c.5882G>A ABCA4 p.C1150del Complex 1 deficiency, mitochondrial respiratory NDUFAF3 G77R chain NDUFA11 c.IVS15G>A TMC1 R34X Epidermolysis bullosa lethalis LAMA3 c.860_861insT c.2942delA p.K594N LAMB3 c.129insA p.Q1083X p.R792X p.Q1083X LAMC2 c.368_373delinsACCAC p.R586X Epidermolysis bullosa simplex KRT5 p.G476D KRT14 p.R125C p.R134C p.W305X Leber congenital amaurosis CRB1 c.3306G>A RDH12 c.377C>T GUCY2D c.387del CRB1 c.4005+1G>A c.4121-4130del CNGA3 G333C Maple syrup urine disease BCKDHA Exon 6 del 9

p.R242X DBT p.V69G p.H391R Meckel/ Joubert syndrome MKS1 p.Q350X MKS3 c.1065+1delG c.IVS10+1delG NPHP6 G1890X TMEM216 c.G230C Mitochondrial depletion syndrome SUCLA2 3272del43ins5 TK2 p.I181N Nonketotic Hyperglycinemia GLDC p.A802V c.2607C>A AMT p.H42R

Persistent hyperinsulinemic hypoglycemia of ABCC8 c.1113insT infancy p.R836X KCNJ11 p.P254L + 88 g >t Retinitis pigmentosa TULP1 c.1495+2_1495+3insT C2ORF71 c.2756_2768del c.556C>T PRCD p.R22X

Severe combined immune deficiency RAG1 L454Q RAG2 C1886T Walker Warburg syndrome POMT2 p.K307fs POMT1 p.L421fs

2. The Molecular basis of Autosomal Recessive Diseases among the Druze

One mutation 10

Argininosuccinic aciduria ASL c.346C>T Arthrogryposis renal dysfunction and cholestasis VPS33B D234H Calcinosis, tumoral with hyperphosphatasemia. GALNT3 c.1524G+1G>A Carbamoyl phosphate synthetase I deficiency CPS1 c.31265C>T Carnitine Palmitoyl transferase deficiency CPT1A p.D454G Cerebrotendinous xanthomatosis CYP27A1 c.85delC Cockayne syndrome ERCC6 c.1034-1035 insT Congenital amegakaryotic thrombocytopenia c-MLP T460C Cystinuria SLC3A1 c.808C>T Ectodermal dysplasia EDAR p.C87R Factor XI deficiency (PTA) FXI p.T386N Glaucoma, congenital CYP1B1 p.R469W Glycogenosis V, myophosphorylase deficiency, PYGM c.1844+1G>A Hypotrichosis with juvenile macular dystrophy CDH3 c.981delG Ichthyosis congenital recessive FLJ39501 W521X Krabbe disease GALC c.1748T>C Laron syndrome, Pituitary dwarfism II GHR 785-1 G>T Mitochondrial depletion syndrome DGUOK c.204delA Niemann Pick C NPC1 c.3347delTC Oxalosis AGTX M195R

More than 1 mutation in one gene

Ataxia telangiectasia ATM c.6672delGG/delTACG c.1339C>T Factor VII deficiency FVII IV52+1G>C p.C310P Ex2C>A Hurler syndrome IDU Ex7C>T exon 8 A>C Mucolipidosis III GNPTAB c.167insC p.G106S Mucolipidosis IV MCOLN1 p.R322X p.R403C Pompe disease GAA p.D404N p.L355P Prolidase deficiency PEPD L368R p.S202F Tay Sachs disease HEXA c.496Cdel p.S279P Wilson disease ATP7B c.3648del6bp W939C 11

Mutations in more than one gene

Epidermolysis bullosa simplex KRT5 p.1467K

KRT14 p.R125H p.Y415C Maple syrup urine disease DBT p.S133X BCKDHA Ser289Leu

3. The Molecular basis of Autosomal Recessive Diseases among the Christian Arabs

One mutation Ataxia telangiectasia ATM c.2284delCT Ceroid lipofuscinosis, 3 CLN2 Y199X Cockayne syndrome CSA p.T322X Complex 1 deficiency, mitochondrial respiratory chain NDUFS2 c.1237T>C Factor VII deficiency FVII p.P24del Maple syrup urine disease BCKDHA p.C29W Sandhoff disease HEXB IVS8 nt5 Sanfilippo A disease SGSH p.R233X

More than one mutation Albinism, oculocutaneous TYR p.G253R p.S50X IVS2-1G p.R299H p.R402X Cone-rod dystrophy c.5460+1G>A ABCA4 p.G1203E c.5882G>A IVS28-15del123bp c.4538insC p.C1150del PROM1 c.1349insT Metachromatic leukodystrophy, late infantile ARSA p.T274M p.R390W c.499+1G>A