3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings.
Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) consists of early bilateral optic atrophy, later development of spasticity, extrapyramidal dysfunction and occasionally cognitive deficits, and urinary excretion of 3-methylglutaconic acid and 3-methylglutaric acid. The presence of the disorder in an Iraqi-Jewish genetic isolate led to mapping of the OPA3 gene to chromosome 19q13.2-q13.3, followed by isolation of the gene itself. OPA3 consists of two exons and codes for a peptide of 179 amino acids. Iraqi-Jewish patients with type III MGA are homozygous for a splice site founder mutation in OPA3 (IVS1-1G>C) which abolishes mRNA expression in fibroblasts. Here we report a novel mutation in OPA3 (320-337del) in a Kurdish-Turkish patient with optic atrophy and 3-methylglutaconic and 3-methylglutaric aciduria, previously carrying the diagnosis of type IV MGA. We conclude that type III MGA occurs in patients of non-Iraqi-Jewish ancestry, and should be considered in patients with type IV MGA that have optic atrophy and ataxia.
Kleta
Robert
R
Section on Human Biochemical Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, MSC 1830, Building 10, Room 9S-241, Bethesda, MD 20892-1830, USA.
Skovby
Flemming
F
Christensen
Ernst
E
Rosenberg
Thomas
T
Gahl
William A
WA
Anikster
Yair
Y
D000293:Adolescent; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics* / Q000473:pathology*; D001483:Base Sequence; D004247:DNA; D005977:Glutarates / Q000652:urine*; D006801:Humans; D007585:Jews; D008279:Magnetic Resonance Imaging; D008297:Male
D005977:Glutarates; C022034:3-methylglutaconic acid; D004247:DNA