TY - JOUR U1 - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed) 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 JF - 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180283/ SN - 0002-9297 SS - 0002-9297 PM - 12696021 VL - 72 IS - 5 SP - 1300 EP - 1307 PB - American Society of Human Genetics ER -