TY  - JOUR
A1  - Ofman, Rob
A1  - Ruiter, Jos P. N.
A1  - Feenstra, Marike
A1  - Duran, Marinus
A1  - Poll-The, Bwee Tien
A1  - Zschocke, Johannes
A1  - Ensenauer, Regina
A1  - Lehnert, Willy
A1  - Sass, Jörn Oliver
A1  - Sperl, Wolfgang
A1  - Wanders, Ronald J. A.
T1  - 2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency is caused by mutations in the HADH2 gene
T2  - Am J Hum Genet. (The American Journal of Human Genetics)
N2  - 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) deficiency is a novel inborn error of isoleucine degradation. In this article, we report the elucidation of the molecular basis of MHBD deficiency. To this end, we purified the enzyme from bovine liver. MALDI-TOF mass spectrometry analysis revealed that the purified protein was identical to bovine 3-hydroxyacyl-CoA dehydrogenase type II. The human homolog of this bovine enzyme is a short-chain 3-hydroxyacyl-CoA dehydrogenase, also known as the "endoplasmic reticulum-associated amyloid-beta binding protein" (ERAB). This led to the identification of the X-chromosomal gene involved, which previously had been denoted "HADH2." Sequence analysis of the HADH2 gene from patients with MHBD deficiency revealed the presence of two missense mutations (R130C and L122V). Heterologous expression of the mutant cDNAs in Escherichia coli showed that both mutations almost completely abolish enzyme activity. This confirms that MHBD deficiency is caused by mutations in the HADH2 gene.
Y1  - 2003
UR  - https://pub.h-brs.de/frontdoor/index/index/docId/3907
UR  - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180283/
SN  - 0002-9297
VL  - 72
IS  - 5
SP  - 1300
EP  - 1307
PB  - American Society of Human Genetics
ER  -