Table 1 Cases with positive molecular findings
From: The clinical utility of rapid exome sequencing in a consanguineous population
ID | Justification for RES | Clinical utility | Variant | OMIM-compatible diagnosis |
|---|---|---|---|---|
Pat-1139 | Decision about liver transplant | Management (candidate for liver transplant), reproductive counseling (25% recurrence risk) | ABCB4:NM_000443:exon6:c.526C > T:p.Arg176Trp | Cholestasis, progressive familial intrahepatic 3 |
Pat-1000 | Decision about termination | Management (prenatal testing), reproductive counseling (increase from 25% to 7/16, see text) | LMOD3:NM_198271:exon2:c.944_945del:p.Leu315GlnfsTer10 | Nemaline myopathy 10 |
Pat-1037 | Decision about management | Management (disease-specific treatment), reproductive counseling (50% recurrence risk) | HMBS:NM_001258208:exon12:c.706-2A > T | Porphyria, acute intermittent, nonerythroid variant |
Pat-1117 | Decision about management | Management (avoid steroid, list for transplant), reproductive counseling (25% recurrence risk) | PLCE1:NM_001165979:exon7:c.2134C > T:p.Gln712Ter | Nephrotic syndrome, type 3 |
Pat-1003 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | ADA2:NM_177405.1:c.724_728del: p.Ser242ProfsTer5 | Vasculitis, autoinflammation, immunodeficiency, hematologic defects syndrome |
Pat-1039 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | GALE:NM_001127621:exon3:c.151C > T:p.Arg51Trp | GALE-related thrombocytopenia (not yet listed in OMIM, see text) |
Pat-1050 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | MYSM1:NM_001085487:exon8:c.1168G > T:p.Glu390Ter | Bone marrow failure syndrome 4 |
Pat-1025 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | MYSM1:NM_001085487:exon7:c.412C > T:p.R138Ter | Bone marrow failure syndrome 4 |
Pat-1001 | Decision about termination | Prognostication | COL25A1:NM_001256074.2:c.1517del:p.Pro506HisfsTer25 | COL25A1-related fetal akinesia (not yet listed in OMIM, see text) |
Pat-1188 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | RAG1:NM_000448:exon2:c.555delG:p.Lys186SerfsTer15 | Severe combined immunodeficiency, B cell-negative |
Pat-1098 | Decision about management | Management (diagnosis-specific guidelines of drugs to avoid), reproductive counseling (50% recurrence risk in male offspring) | G6PD:NM_000402:exon6:c.653C > T:p.Ser218Phe | Anemia, nonspherocytic hemolytic, due to G6PD deficiency |
Pat-1187 | Decision about liver transplant | Management (candidate for liver transplant), reproductive counseling (25% recurrence risk) | ABCB4:NM_000443:exon13:c.1378A > T:p.Ile460Phe | Cholestasis, progressive familial intrahepatic 3 |
Pat-1006 | Decision about liver transplant | Prognostication (progressive neurodegeneration), management (not candidate for liver transplant), reproductive counseling (25% recurrence risk) | SCYL1:NM_020680:exon10:c.1386 + 1G > T | Spinocerebellar ataxia, autosomal recessive 21 |
Pat-1028 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | RAB27A:NM_004580:exon4:c.244C > T:p.Arg82Cys | Griscelli syndrome, type 2 |
Pat-1052 | Decision about BMT | Management (rule out as a BMT donor, diagnosis-specific screening), reproductive counseling (7/16 recurrence risk) | BRCA2:NM_000059:exon19:c.8452G > T:p.Val2818Phe DCAF17:NM_001164821:exon4:c.436delC: p.Ala147HisfsTer9 | Fanconi anemia, complementation group D1, Woodhouse-Sakati syndrome, dual diagnosis |
Pat-1064 | Decision about liver transplant | Management (not candidate for liver transplant), reproductive counseling (25% recurrence risk) | MPV17:NM_002437:exon4:c.279 + 1G > T | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) |
Pat-1078 | Decision about DNR | Management (palliative care), reproductive counseling (25% recurrence risk) | ACOX1: NM_007292:exon12:c.1728 + 1G > A | Peroxisomal acyl-CoA oxidase deficiency |
Pat-1043 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | JAK3: NM_000215.3:exon2:c.115dupC:p.Gln39ProfsTer13 | SCID, autosomal recessive, T-negative/B-positive type |
Pat-1042 | Decision about management | Prognostication (life-long disease), management (avoid intestinal biopsy, plan lifelong TPN), reproductive counseling (25% recurrence risk) | EPCAM:NM_002354:exon5:c.499dupC:p.Gln167ProfsTer21 | Diarrhea 5, with tufting enteropathy, congenital |
Pat-1023 | Decision about liver transplant | Management (candidate for liver transplant), reproductive counseling (25% recurrence risk) | ATP7B:NM_001005918:exon17:c.3574delC:p.Gln1192ArgfsTer6 | Wilson disease |
Pat-1038 | Decision about liver transplant | Management (disease-specific treatment, not candidate for liver transplant), reproductive counseling (25% recurrence risk) | AKR1D1:NM_001190906:exon2:c.148C > T:p.Arg50Ter | Bile acid synthesis defect, congenital, 2 |
Pat-1045 | Decision about DNR | Management (disease-directed investigation with urine organic acid and acylglycine profile showing severe ethylmalonic aciduria and elevated isobuturylglycine and isovalerylglycine), reproductive counseling (25% recurrence risk) | ETFB:NM_001014763:exon2:c.547C > T:p.Pro183Ser | Glutaric acidemia IIB |
Pat-1047 | Decision about management | Prognostication (once regression ensues, it is irreversible), management (palliative care), reproductive counseling (25% recurrence risk) | SLC25A42:NM_001321544:exon8:c.871A > G:p.Asn291Asp | Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression |
Pat-1053 | Decision about DNR | Management (palliative care), reproductive counseling (only 25% probability of a healthy child) | FGFR3:NM_000142:exon9:c.1138G > A:p.Gly380Arg | Camptodactyly, tall stature, hearing loss syndrome; CATSHLS/autosomal recessive achondroplasia |
Pat-1069 | Decision about BMT | ,Management (candidate for BMT), reproductive counseling (recurrence risk) | ELANE:NM_001972:exon5:c.640G > A:p.Gly214Arg | Neutropenia, severe congenital |
Pat-1060 | Decision about DNR | Management (not candidate for BMT), reproductive counseling (7/16 recurrence risk) | RAG1:NM_000448:exon2:c.554delG: p.Lys186SerfsTer15 TXNDC15:NM_001350735:exon3:c.499C > T:p.Arg167Trp | Severe combined immunodeficiency, B cell-negative |
Pat-1054 | Decision about BMT | Management (candidate for BMT), reproductive counseling (50% recurrence risk) | RTEL1:NM_001283009.2:c.3271_3273delGAC:p.Asp1091del | Dyskeratosis congenita |
Pat-1058 | Decision about DNR | Management (palliative care), reproductive counseling (25% recurrence risk) | OSTM1:NM_014028:exon2:c.415_416del:p.Gln140GlufsTer11 | Osteopetrosis, autosomal recessive 5 |
Pat-1057 | Decision about liver transplant | Management (not candidate for liver transplant, diagnosis-specific therapy), reproductive counseling (25% recurrence risk) | GALT:NM_001258332:exon6:c.364C > T:p.Arg122Cys | Galactosemia |
Pat-1192 | Decision about BMT | Management (not suitable as a BMT donor, diagnosis-specific screening), reproductive counseling (25% recurrence risk) | ATM:NM_000051:exon5:c.381delA:p.Val128Ter | Ataxia-telangiectasia |
Pat-1067 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | RAG2:NM_00536:exon2:c.110C > T:p.Pro37Leu | Severe combined immunodeficiency, B cell-negative |
Pat-1074 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | ZAP70:NM_001079:exon4:c.492delC p.His165ThrfsTer4 | Immunodeficiency, 48 |
Pat-1065 | Decision about management | Management (palliative care), reproductive counseling (25% recurrence risk) | PDHB:NM_000925:exon1:c.1A > G:p.? | Pyruvate dehydrogenase E1-beta deficiency |
Pat-1062 | Decision about DNR | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | LIPA:NM_000235:exon4:c.260G > T:p.Gly87Val | Wolman disease |
Pat-1099 | Decision about BMT | Management (not candidate for BMT), reproductive counseling (25% recurrence risk) | OSTM1:NM_014028:exon2:c.415_416del: p.Gln140GlufsTer11 | Osteopetrosis, autosomal recessive 5 |
Pat-1076 | Decision about management | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | KCNJ11:NM_000525:exon1:c.112A > G:p.Lys38Glu | Hyperinsulinemic hypoglycemia, familial, AR |
Pat-1072 | Decision about liver transplant | Management (not a candidate for liver transplant), reproductive counseling (25% recurrence risk) | ANKS6:NM_173551:exon11:c.2142G > T:p.Lys714Asn | Nephronophthisis, 16 |
Pat-1085 | Decision about management | Management (diagnosis-specific screening and prophylaxis), reproductive counseling (25% recurrence risk) | C8B:NM_000066:exon9:c.1282C > T:p.Arg428Ter | C8 deficiency, type II |
Pat-1184 | Decision about management | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | CYP19A1:NM_001347256.2:exon3:c.343C > T:p.Arg115Ter | Aromatase deficiency |
Pat-1101 | Decision about liver transplant | Management (candidate for liver transplant), reproductive counseling (25% recurrence risk) | ABCB4:NM_000443:exon23:c.2906G > A:p.Arg969His | Cholestasis, progressive familial intrahepatic 3 |
Pat-1087 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | AK2:NM_001319142:exon5:c.398G > C:p.Arg133Pro | Reticular dysgenesis |
Pat-1104 | Decision about DNR | Management (palliative care), reproductive counseling (minimal recurrence risk in parents) | ACTA1:NM_001100:exon4:c.593G > A:p.Arg198His | Myopathy, actin, congenital, with cores |
Pat-1094 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | JAK3:NM_000215:exon3:c.307C > T:p.Arg103Cys and JAK3:NM_000215:exon6:c.678_679del:p.Cys227ProfsTer49 | SCID, autosomal recessive, T-negative/B-positive type |
Pat-1106 | Decision about management | Management (diagnosis-specific therapy), reproductive counseling (25% recurrence risk) | SLC25A15:NM_014252.4:c.-69-41_55 + 58del | Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome |
Pat-1110 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | STXBP2:NM_001127396:exon16:c.1421C > T:p.Pro474Leu | Hemophagocytic lymphohistiocytosis, familial, 5, with or without microvillus inclusion disease |
Pat-1141 | Decision about liver transplant | Management (not candidate for liver transplant), reproductive counseling (25% recurrence risk) | MPV17:NM_002437:exon4:c.279 + 1G > T | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) |
Pat-1113 | Decision about liver transplant | Management (not candidate for liver transplant), reproductive counseling (25% recurrence risk) | MPV17:NM_002437:exon4:c.279 + 1G > T | Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) |
Pat-1114 | Decision about liver transplant | Management (candidate for liver transplant), reproductive counseling (25% recurrence risk) | ATP7B:NM_001005918:exon17:c.3574delC:p.Gln1192ArgfsTer6 | Wilson disease |
Pat-1116 | Decision about liver transplant | Management (candidate for liver transplant), reproductive counseling (25% recurrence risk) | AIRE:NM_000383:exon10:c.1192delC:p.Pro398ArgfsTer82 | Autoimmune polyendocrinopathy syndrome, type I, with or without reversible metaphyseal dysplasia |
Pat-1119 | Decision about management | Management (avoid diazoxide, good candidate for pancreatectomy), reproductive counseling (25% recurrence risk) | KCNJ11:NM_000525:exon1:c.101G > A:p.Arg34His | Hyperinsulinemic hypoglycemia, familial, AR |
Pat-1120 | Decision about DNR | Management (palliative care), reproductive counseling (25% recurrence risk) | PC:NM_022172:exon6:c.736G > A:p.Glu246Lys and PC:NM_022172:exon11:c.1486C > T:p.Arg496Trp | Pyruvate carboxylase deficiency |
Pat-1131 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | PNP:NM_000270:exon2:c.12-1G > C | Immunodeficiency due to purine nucleoside phosphorylase deficiency |
Pat-1143 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | RAB27A:NM_183234.2:c.467 + 1_467 + 4del | Griscelli syndrome, type 2 |
Pat-1142 | Decision about management | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | MTHFR:NM_001330358:exon7:c.1252C > T:p.Arg418Cys | Homocystinuria |
Pat-1138 | Decision about management | None | NIPBL:NM_015384:exon10:c.3060_3063del:p.Glu1021ThrfsTer22 | Cornelia de Lange syndrome 1 |
Pat-1156 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | CYBA:NM_000101.4:exon4:c.261C > A: p.Tyr87Ter | Chronic granulomatous disease 4, autosomal recessive |
Pat-1150 | Decision about management | Management (diagnosis-specific management), reproductive counseling (25% recurrence risk) | PTF1A:NM_178161.3:exon1:c.571C > A:p.Pro191Thr | Pancreatic and cerebellar agenesis |
Pat-1083 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | RAG1:NM_000448.3:exon2:c.2210G > A:p.Arg737His | Severe combined immunodeficiency, B cell-negative |
Pat-1153 | Decision about management | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | SCNN1A:NM_001159575.1:exon4:c.944 + 1G > A | Pseudohypoaldosteronism, type I |
Pat-1152 | Decision about management | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | ABCC8:NM_000352.6:exon4:c.563A > G:p.Asn188Ser | Diabetes mellitus, permanent neonatal 3 |
Pat-1154 | Decision about liver transplant | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | AKR1D1:NM_001190906.2:exon8:c.817 T > C:p.Trp273Arg | Bile acid synthesis defect, congenital, 2 |
Pat-1159 | Decision about management | Management (diagnosis-specific treatment), reproductive counseling (50% recurrence risk) | RB1:NM_000321.3:c.1450_1451del:p.Met484ValfsTer8 | Retinoblastoma |
Pat-1157 | Decision about BMT | Management (not candidate for BMT), reproductive counseling (25% recurrence risk) | OSTM1:NM_014028.4:exon2:c.415_416del: p.Gln140GlufsTer11 | Osteopetrosis, autosomal recessive 5 |
Pat-1158 | Decision about BMT | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | RAG2:NM_000536.4:exon2:c.686G > C:p.Arg229Pro | Severe combined immunodeficiency, B cell-negative |
Pat-1160 | Decision about BMT | Reproductive counseling (25% recurrence risk) | GNS:NM_002076.4:exon6:c.732C > A: p.Tyr244Ter | Mucopolysaccharidosis type IIID |
Pat-1002 | Decision about management | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | RFXANK:NM_134440.2:c.268 + 1G > C | Bare lymphocyte syndrome, type II, complementation group B |
Pat-1090 | Decision about BMT | Reproductive counseling (25% recurrence risk) | DIAPH1:NM_001079812:exon15:c.2305C > T: p.Gln769Ter | Seizures, cortical blindness, microcephaly syndrome |
Pat-1029 | Decision about management | Management (candidate for BMT), reproductive counseling (25% recurrence risk) | SMARCD2:NM_001098426:exon11:c.1429C > T:p.Arg477Ter | Specific granule deficiency 2 |
Pat-1011 | Decision about management | Management (diagnosis-specific screening), reproductive counseling (50% recurrence risk) | TTN:NM_003319:exon166:c.64806G > A: p.Trp21602Ter | Cardiomyopathy, dilated, 1G |
Pat-1013 | Decision about management | Management (candidate for BMT), recurrence risk (50% recurrence risk for male offspring) | SH2D1A:NM_001114937:exon1:c.23A > C:p.His8Pro | Lymphoproliferative syndrome, X-linked, 1 |
Pat-1075 | Decision about DNR | Management (palliative care), reproductive counseling (25% recurrence risk) | PEX5:NM_001351132.2:c.1578 T > G;p.Asn526Lys | Peroxisome biogenesis disorder, 2A (Zellweger) |
Pat-1121 | Decision about management | Reproductive counseling (25% recurrence risk) | PRF1:NM_001083116:exon3:c.880delC: p.Gln294LysfsTer36 | Hemophagocytic lymphohistiocytosis, familial, 2 |
Pat-1146 | Decision about management | Management (avoid selumetinib, diagnosis-specific surveillance), reproductive counseling (50% recurrence risk) | SMARCB1:NM_001317946:exon8:c.1145 + 2 T > C | Schwannomatosis |
Pat-1145 | Decision about management | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | MEFV:NM000243:exon10:c.2082G > A:p.Met694Ile | Familial Mediterranean fever |
Pat-1151 | Decision about management | Prognostication (natural history), reproductive counseling (25% recurrence risk) | ISCA2:NM_194279.4:exon3:c.229G > A:p.Gly77Ser | Multiple mitochondrial dysfunctions syndrome 4 |
Pat-1161 | Decision about management | Management (candidate for BMT), reproductive counseling (50% recurrence risk in male offspring) | FOXP3:NM_001114377.2:exon11:c.1085G > A:p.Arg362Gln | Immunodysregulation, polyendocrinopathy, enteropathy, X-linked |
Pat-1140 | Decision about liver transplant | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | ATP7B:NM_001330579:exon6:c.1978 T > C:p.Ser660Pro | Wilson disease |
Pat-1021 | Decision about termination | Management (prenatal testing), reproductive counseling (recurrence risk) | ZDHHC15:NM_001146256:exon4:c.421A > G:p.Met141Val and TYR:NM_000372:exon4:c.1322delC:p.Ser | Albinism oculocutaneous |
Pat-1088 | Decision about BMT | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | TCN2:NM_001184726:exon1:c.64 + 4A > T | Transcobalamin II deficiency |
Pat-1132 | Decision about DNR | Management (diagnosis-specific treatment), reproductive counseling (25% recurrence risk) | SLC52A3:NM_033409:exon2:c.211G > A:p.Glu71Lys | Brown-Vialetto-Van Laere syndrome 1 |