L-2-Hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1.
l-2-Hydroxyglutaric aciduria (l-2-HGA) is characterized by progressive deterioration of central nervous system function including epilepsy and macrocephaly in 50% of cases, and elevated levels of l-2-hydroxyglutaric acid in urine, blood and cerebrospinal fluid (CSF). Nuclear magnetic resonance imaging shows distinct abnormalities. We report the identification of a gene for l-2-HGA aciduria (MIM 236792) using homozygosity mapping. Nine homozygous mutations including three missense mutations, two nonsense mutations, two splice site mutations and two deletions were identified in the gene C14orf160, localized on chromosome 14q22.1, in 21 patients from one non-consanguineous and 14 consanguineous Turkish families. We propose to name the gene duranin. Duranin encodes a putative mitochondrial protein with homology to FAD-dependent oxidoreductases. The functional role of this enzyme in intermediary metabolism in humans remains to be established.
Topçu
Meral
M
Department of Pediatrics, Child Neurology, Hacettepe University Medical Faculty, Ankara, Turkey.
Jobard
Florence
F
Halliez
Sophie
S
Coskun
Turgay
T
Yalçinkayal
Cengiz
C
Gerceker
Filiz Ozbas
FO
Wanders
Ronald J A
RJ
Prud'homme
Jean-François
JF
Lathrop
Mark
M
Ozguc
Meral
M
Fischer
Judith
J
D000293:Adolescent; D000328:Adult; D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000201:enzymology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002883:Chromosomes, Human, Pair 14; D003241:Consanguinity; D005260:Female; D005977:Glutarates / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine*; D006801:Humans; D015810:Linkage Disequilibrium; D008279:Magnetic Resonance Imaging; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D014421:Turkey
D005977:Glutarates; D024101:Mitochondrial Proteins; C019417:alpha-hydroxyglutarate; D010088:Oxidoreductases; D000429:Alcohol Oxidoreductases; C506763:L2HGDH protein, human