title: OPA3 mutation screening in patients with unexplained 3-methylglutaconic aciduria.
abstract: We have screened 13 patients with neurological abnormalities and 3-methylglutaconic aciduria (3MGA) for mutations in the OPA3 gene, which are known to be the cause of Costeff syndrome (optic atrophy, chorea and spasticity; type III 3MGA). We aimed to explore whether mutations in the OPA3 gene are present in patients with 3MGA but without classic Costeff syndrome. OPA3 mutations (IVS1-1G>C) were identified in 2 patients with the classic phenotype of type III 3MGA, but not in the other 11 patients with differing non-Costeff phenotypes associated with developmental delay and neurological signs and symptoms as described. We identified a previously described sequence variation in the OPA3 gene (c.231T>C) in 12/13 patients. The alteration was homozygous in 8/12 and heterozygous in 4/12. This alteration was also found in 60 of 98 normal control alleles. In a single patient, a novel sequence variation in the 5' UTR was identified, (c.-38A>G). Our studies suggest that the c.231T>C sequence variation is of no clinical significance, whereas the significance of the 5' UTR sequence variation remains open to speculation. Our study of the OPA3 gene in patients with 3MGA without Costeff syndrome suggests that mutations in OPA3 are not a common cause of 3MGA in the absence of signs of Costeff syndrome.
authors.affiliation: Western Sydney Genetics Program, The Children's Hospital at Westmead, Sydney, NSW, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Neas
authors.forename: B
authors.initials: B
authors.lastname: Bennetts
authors.forename: K
authors.initials: K
authors.lastname: Carpenter
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: E P
authors.initials: EP
authors.lastname: Kirk
authors.forename: M
authors.initials: M
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Kelley
authors.forename: I
authors.initials: I
authors.lastname: Baric
authors.forename: J
authors.initials: J
authors.lastname: Christodoulou
mesh_terms: D020121:5' Untranslated Regions; D000293:Adolescent; D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics; D014644:Genetic Variation; D005977:Glutarates / Q000097:blood*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013577:Syndrome
chemical_list: D020121:5' Untranslated Regions; D005977:Glutarates; C443108:OPA3 protein, human; D011506:Proteins; C022034:3-methylglutaconic acid