Gene (Isoform) | Variants (PMID) | Diagnosis (MIM) | Comments |
---|---|---|---|
Mitochondrial inheritance | |||
tRNA Ala | m.5591G > Ab (16476954) | MTTA (590000) | Failure to thrive, ptosis, myopathy, normal mitochondrial studies on muscle biopsy. |
ND5 | m.13513G > A (p.D393N)b (12509858) | MTND5 (516005) | Developmental regression, dysmorphic features, esotropia, chorioretinal atrophy, seizure, left ventricular hypertrophy, renal insufficiency, brain image suggestive of Leigh syndrome. |
X-Linked inheritance | |||
PDHA1 (NM_000284) | c.787C > G (p.R263G) (1508605) | PDHAD (312170) | Brain image suggestive of Leigh syndrome; low complex II (succinate dehydrogenase) activity in the fibroblasts. Two heterozygous (‘cis’ configuration) novel missense variants, c.321C > G (p.1107 M) and c.338A > T (p.N113I), in SDHA were found in patient and father. |
Autosomal recessive inheritance | |||
FBXL4 (NM_012160) | c.1067delG (p.G356fs) (23993194) | MTDPS13 (615471) | Developmental regression, hypotonia, failure to thrive, microcephaly, lactic acidosis, normal fibroblast mitochondrial studies. Three siblings died in infancy. |
C10orf2 (NM_021830) | c.1198C > T (p.R400C) (21364701) | MTDPS7 (271245) | Developmental regression, hearing loss, scoliosis, reduced activities of complexes I & IV in myocytes; normal activities in fibroblasts. Two cousins with Leigh disease. |
MTHFR (NM_005957) | c.1596C > G(p.Y532) (a) | MTHFRD (236250) | Progressive encephalopathy, seizure, cerebral venous thrombosis, gangrenous like bullous formation in the leg, congenital heart disease, ↑homocysteine, ↓methionine. |
PYCR2 (NM_013328) | c.28C > T(p.Q10X) (a) | HLD10 (616420) | Developmental regression, failure to thrive, seizure, microcephaly, severe demyelination, thin corpus callosum. |
c.796C > T(p.R266X) (a) | Developmental delay, hypotonia, failure to thrive, microcephaly, thin corpus callosum, delayed myelination. | ||
HEXA (NM_000520) | c.2 T > C | Tay-Sachs (268800) | Developmental regression, failure to thrive, seizure disorders, dystonia, feeding difficulties constipation. Diagnosis confirmed by enzyme analysis. |
HEXB (NM_000521) | c.826_829del (p.E276fs) | Sandhoff (268800) | Developmental regression, failure to thrive, feeding difficulties, seizure, and vision loss. |
SUMF1 (NM_182760) | c.691dupT (p.W231fs) c.689A > G (p.E230ZG) | MSD (272200) | Developmental delay, seizure, hepatomegaly, delayed myelination, ↑urine sulfatide, ↑urine heparan sulphate. |
UROC1 (NM_144639) | c.855G > A (p.W285X) (a) | UROCD (276880) | Intellectual disabilities, attention deficit and hyperactivity disorder, hyperextensible joints, ↑imidazole propionate. |
TBX19 (NM_005149) | c.604-1G > C (a) | IAD (201400) | Intellectual disabilities, congenital hypothyroidism, two sisters died in infancy with hypoglycemia. |
HSD3B7 (NM_025193) | c.45_46del (p.G17fs) (12679481) | CBAS1 (607765) | Neonatal cholestasis, hepatosplenomegaly, hypotonia, failure to thrive. |