A novel mutation of the human 7-dehydrocholesterol reductase gene reduces enzyme activity in patients with holoprosencephaly

Yhong Hee Shim, Soo Han Bae, Jai Hyun Kim, Kyu Rae Kim, Chong Jai Kim, Young Ki Paik

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7 Citations (Scopus)


Defects in cholesterol biosynthesis genes are recognized as a leading cause for holoprosencephaly (HPE). Previous reports suggest that mutations of human 7-dehydrocholesterol reductase (Dhcr7), which catalyzes the final step of cholesterol biosynthesis, may cause HPE [Clin. Genet. 53 (1998) 155]. To determine whether Dhcr7 mutations are involved in HPE pathogenesis, we analyzed the sequence of exon 9, which contains both a catalytic domain and a mutational hot spot. We examined 36 prematurely terminated fetuses with HPE at their gestation ages in the range from 21 to 33 weeks by single strand conformation polymorphism analysis and DNA sequencing. A novel missense mutation was identified: G344D. Dhcr7 enzyme assays using overexpressed recombinant mutant proteins revealed altered enzyme activity. Mutant G344D harbored less than 50% of enzyme activity compared with the control. Two previously reported mutations, R404C and G410S, abolished enzyme activity. These results suggest that mutation of the Dhcr7 gene is involved in HPE pathogenesis.

Original languageEnglish
Pages (from-to)219-223
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number1
Publication statusPublished - 2004 Feb 27

Bibliographical note

Funding Information:
This work was supported by Grant No. R04-2002-000-20096-0 (2003) from the Basic Research Program of the Korea Science and Engineering Foundation (to Y.H.S.), from BioGreen 21 Program, Rural Development Administration, Republic of Korea, and the Korean Ministry of Health and Welfare (to Y.K.P.). We are grateful to Ms. Ji-Young Jang for her technical assistance in the initial stage of this work and to Dr. Jung-Sun Kim at Asan Medical Center for her enthusiastic support of this study.

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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