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Biochemical and molecular analyses in three patients with 3‐hydroxy‐3‐methylglutaric aciduria
Author(s) -
Pospíšilová E.,
Mrázová L.,
Hrdá J.,
Martincová O.,
Zeman J.
Publication year - 2003
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1025169210121
Subject(s) - heterozygote advantage , compound heterozygosity , proband , genotype , mutation , genetics , gene , human genetics , endocrinology , medicine , biology , chemistry , microbiology and biotechnology
Two methods, spectrophotometry and HPLC, were compared in the analyses of 3‐hydroxy‐3‐methylglutaryl‐CoA lyase (HL) activity in three unrelated Czech patients with 3‐hydroxy‐3‐methylglutaric (HMG) aciduria and their family members. The HL activities in cultured fibroblasts and/or isolated lymphocytes of probands were below the detection limits of the methods used. Both methods were also suitable for recognition of all heterozygotes in affected families. We searched for pathogenic mutations in the HL gene. Molecular analyses revealed that two patients are homozygous for known mutation H233R and R41Q, respectively, whereas the third patient is a compound heterozygote for the mutation H233R and a novel mutation Pro9fs(−1). This study expands the knowledge of the genotypic variability of the HMG aciduria.