Table 3 Confirmed genetic diseases by WES, n = 17
Gene (Isoform) | Variants (PMID) | Diagnosis (MIM) | Comments |
|---|---|---|---|
X-Linked Inheritance | |||
PAK3 (NM_002578) | c.1279 T > C (p.Y427H) | MRX30 (300558) | Intellectual disabilities, macrocephaly, obesity. |
Autosomal Dominant Inheritance | |||
BRAF (NM_004333) | c.1914 T > G (p.D638E) (19206169) | CFC1 (115150) | Cortical blindness, seizures, stridor, constipation and developmental delay. |
DYNC1H1 (NM_001376) | c.10973G > A (p.G3658E) | MRD13 (614563) | Developmental regression, seizure, microcephaly, cataract, lissencephaly, pachygyria, grey matter heterotopia, hypoplasia of the corpus callosum. |
ARID1B (NM_020732) | c.4870C > T (p.R1624X) (a) | Coffin-Siris (135900) | Mucopolysaccharidosis suspected clinically. |
ARID1B (NM_020732) | c.3689 + 1G > C | Coffin-Siris (135900) | Global developmental delay, failure to thrive, acute encephalopathy with hypoglycemia and metabolic acidosis. |
MYBPC3 (NM_000256) | c.776delinsTT (p.A259fs) | CMD1MM (615396) | Dilated cardiomyopathy. |
Autosomal Recessive Inheritance | |||
SNX10 (NM_001199835) | c.112-1G > C | OPTB8 (615085) | Central hypotonia, optic atrophy, osteopetrosis, pulmonary hypoplasia, hyperpigmented macules. |
TRAPPC11 (NM_199053) | c.2938G > A (p.G980R) (23830518) | LGMD2S (615356) | Developmental delay, head nodding, hypotonia, ↑CPK, ↑plasma phenylalanine, normal CSF neurotransmitters. Homozygous c.362 T > C (p.I121T) variant in COQ9 (normal muscle coenzyme Q10 activity). |
PCSK1 (NM_000439) | c.1312C > T (p.R438X) | Proprotein convertase 1/3 deficiency (600955) | Brain hemorrhage, congenital diarrhea. |
ERCC5 (NM_000123) | c.205C > T (p.R69X)(a) | Cockayne (278780) | Hypotonia, developmental delay and seizure. Clinically suspected to have MLCD. |
AHI1 (NM_017651) | c.1051C > T (p.R351X) (15322546) | Joubert syndrome-3 (608629) | Intellectual disability, hypotonia, repetitive hand movements, brain atrophy. |
PRX (NM_181882) | c.1090C > T (p.R364X) (21741241) | Dejerine-Sottas (145900) | Abnormal gait, hearing loss, loss of dexterity in hands, scoliosis. |
TREX1 (NM_003629) | c.341G > A (p.R114H) (21270825) | RVCL (192315) | Cognitive impairment, hypotonia, joint contracture, glaucoma, brain atrophy, sibling died with the same features. |
DOK7 (NM_173660) | c.1124_1127dup (p.A378fs) & c.1457dup (p.A487fs) (16917026) | Myasthenia, limb-girdle (254300) | Hypotonia, myopathic changes in proximal muscles. |
ADD3 (NM_016824) | c.1100G > A (p.G367D) (23836506) | Adducin-gamma (601568) | Developmental delay, central hypotonia and peripheral spasticity, cortical brain atrophy, delayed myelination of white matter. |
RECQL4 (NM_004260) | c.1000G > T (p.E334X)(a) | RTS (268400) | Premature, intrauterine growth retardation, dry skin, clinically suspected to have MOPD2. |
IKBKB (NM_001556) | c.849G > A (p.W283X)(a) | IMD15 (615592) | Failure to thrive, recurrent infections, two sibling died with the same presentation. |