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Mutations in phenotypically mild D ‐2‐hydroxyglutaric aciduria
Author(s) -
Struys Eduard A.,
Korman Stanley H.,
Salomons Gajja S.,
Darmin Patricia S.,
Achouri Younes,
Van Schaftingen Emile,
Verhoeven Nanda M.,
Jakobs Cornelis
Publication year - 2005
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20559
Subject(s) - missense mutation , phenotype , mutation , asymptomatic , mutant , gene , genetics , medicine , biology
D ‐2‐hydroxyglutaric aciduria is a neurometabolic disorder with mild and severe phenotypes. Recently, we reported pathogenic mutations in the D ‐ 2 ‐ hydroxyglutarate dehydrogenase gene as the cause of the severe phenotype of D ‐2‐hydroxyglutaric aciduria in two patients. Here, we report two novel pathogenic mutations in this gene in one patient with a mild presentation and two asymptomatic siblings with D ‐2‐hydroxyglutaric aciduria from two unrelated consanguineous Palestinian families: a splice error (IVS4‐2A→G) and a missense mutation (c.1315A→G;p.Asn439Asp). Overexpression of this mutant protein showed marked reduction of the enzyme activity. Ann Neurol 2005