Table 2.
Diagnostic findings and phenotypes of patients who underwent clinical genome sequencing
| Gene | Variants | Inheritance pattern | Diagnosis (OMIM) | Signs and symptoms | |
|---|---|---|---|---|---|
| 1 | ZEB2 £ | het c.73+1del | De novo (AD) | Mowat–Wilson syndrome (235730) | Microcephaly, Hirschsprung, hypogammaglobulinemia, lymphopenia, fever |
| 4 | ACTG1 | het c.628C>T (p.Arg210Cys) | De novo (AD) | Baraitser–Winter syndrome 2 (614583) | Microcephaly with brain abnormalities, DD, HL, and foot and hip abnormalities |
| 6 | KPTN | het c.714_731dup | AR | Intellectual disability (615637) | Macrocephaly, intractable epilepsy, ASD, GDD, hypotonia, hypoglycemia, dysmorphia |
| 6 | KPTN | het c.394+1G>A | |||
| 8 | TBL1XR1 | het c.1336T>G (p.Tyr446Asp) | De novo (AD) | Pierpont syndrome (602342) | FTT, hypotonia, GDD, cleft, laryngeal cleft, dysmorphisms, HL, abnormality of the optic nerve |
| 9 | MTATP6 | homoplasmic m.8993T>G | MT | Leigh syndrome (256000) | Abnormal activity of mitochondrial respiratory chain, GDD, lactic acidosis, hypotonia |
| 12 | MYH3 | het c.5355_5357del (p.Lys1785del) | AR?/AD | Arthrogryposis, spondylocarpotarsal synostosis syndrome (178110) | Distal arthrogryposis, antecubital pterygium, popliteal pterygium, cleft palate, scoliosis, rib fusion |
| 12 | MYH3 | het c.5263_5265del (p.Lys1755del) | |||
| 15 | ATL1 | het p.Arg403Pro | De novo (AD) | Spastic paraplegia (182600) | Dystonia, hypertonia, FTT, adducted thumb, GDD, spasticity |
| 24 | ACTA1 | het c.49G>A (p.G17S) | De novo (AD) | Nemaline myopathy (161800) | Cryptorchidism, contractures, microretrognathia, polyhydramnios |
| 29 | TCF12 | het c.1035+5G>A | De novo (AD) | Craniosynostosis (615314) | Seizures, GDD, Angelman-like syndrome, coarctation of the aorta, and laryngeal cleft |
| 31 | WDR73 | homo c.888delT | AR | Galloway–Mowat spectrum (251300) | Abnormal retinal pigmentation, FTT, focal segmental glomerulosclerosis, HL, microcephaly, seizures |
| 31 | COMP | het c.1279_1291del | AD | Multiple epiphyseal dysplasia (32400) | |
| 33 | BBS1 | homo c.1169T>G (p.M390R) | AR | Bardet–Biedl syndrome (209900) | Abnormal behavior, abnormal nasal base, brachycephaly, deep set eyes, heterotopia, ID, polydactyly |
| 42 | ECHS1 | het c.518C>T (p.A173V) | AR | Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (616277) | Dystonia, mitochondrial encephalopathy, pallidal degeneration |
| 42 | ECHS1 | het exons 6-8 del | |||
| 44 | BICD2 | het c.2100C>G (p.N700K) | De novo (AD) | Spinal muscular atrophy (615290) | Akinesia, arthrogryposis multiplex congenita, fetal akinesia sequence |
| 47 | AARS2 | het exons 5-7 del | AR | Combined oxidative phosphorylation deficiency 8 (614096) | Abnormality of the corpus callosum, dilated cardiomyopathy, lactic acidemia |
| 47 | AARS2 | het c.1738C>T, p.R580W | |||
| 49 | MED13L | het c.2591T>A, p.Met864Lys | De novo (AD) | Mental retardation and distinctive facial features with cardiac defects (616789) | Dysmorphia, cardiomegaly, coarctation of aorta, hydrops fetalis, hypoplastic left heart, polymicrogyria |
| 70 | FBN1 £ | het c.5918A>G (p.D1973G) | AD | Marfan syndrome (154700) | Arrhythmia, mitral valve prolapse, myocardial infarction, LQTS, syncope |
| 71 | SCN1A | het c.4456T>G (p.F1486V) | De novo (AD) | Early infantile epileptic encephalopathy 6 (607208) | Hip dislocation, Epileptic encephalopathy, GDD, Heterotopia, Seizures, Spasticity |
| 72 | SMC1A | hemi c.52C>T (p.R18*) | X-linked | Cornelia de Lange syndrome (300590) | ASD, dysphagia, GDD, microcephaly, seizures, status epilepticus, visual impairment |
| 78 | TRPS1 | het c.787del (p.Leu263Cysfs*53) | De novo (AD) | Trichorhinophalangeal syndrome (190350) | 2–3 toe syndactyly, ASD, bulbous nose, hallux valgus, high palate, hypertelorism, macrocephaly, nystagmus, obesity, epicanthal folds, retrognathia, seizures |
AD autosomal dominant, AR autosomal recessive, MT mitochondrial, ID intellectual disability, DD developmental delay, GDD global developmental delay, FTT failure to thrive, HL hearing loss, ASD autism spectrum disorder,LQTS long QT syndrome
The £ sign distinguishes TRIO or DUO NGS run with siblings vs parental samples