2016年10月
Mutations in SDR9C7 gene encoding an enzyme for vitamin A metabolism underlie autosomal recessive congenital ichthyosis
HUMAN MOLECULAR GENETICS
- 巻
- 25
- 号
- 20
- 開始ページ
- 4484
- 終了ページ
- 4493
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1093/hmg/ddw277
- 出版者・発行元
- OXFORD UNIV PRESS
Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of hereditary skin disorder characterized by an aberrant cornification of the epidermis. ARCI is classified into a total of 11 subtypes (ARCI1-ARCI11) based on their causative genes or loci. Of these, the causative gene for only ARCI7 has not been identified, while it was previously mapped on chromosome 12p11.2-q13.1. In this study, we performed genetic analyses for three Lebanese families with ARCI, and successfully determined the linkage interval to 9.47Mb region on chromosome 12q13.13-q14.1, which was unexpectedly outside of the ARCI7 locus. Whole-exome sequencing and the subsequent Sanger sequencing led to the identification of missense mutations in short chain dehydrogenase/ reductase family 9C, member 7 (SDR9C7) gene on chromosome 12q13.3, i. e. two families shared an identical homozygous mutation c.599T> C (p.Ile200Thr) and one family had another homozygous mutation c.214C> T (p.Arg72Trp). In cultured cells, expression of both the mutant SDR9C7 proteins was markedly reduced as compared to wild-type protein, suggesting that the mutations severely affected a stability of the protein. In normal human skin, the SDR9C7 was abundantly expressed in granular and cornified layers of the epidermis. By contrast, in a patient's skin, its expression in the cornified layer was significantly decreased. It has previously been reported that SDR9C7 is an enzyme to convert retinal into retinol. Therefore, our study not only adds a new gene responsible for ARCI, but also further suggests a potential role of vitamin A metabolismin terminal differentiation of the epidermis in humans.
- リンク情報
- ID情報
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- DOI : 10.1093/hmg/ddw277
- ISSN : 0964-6906
- eISSN : 1460-2083
- PubMed ID : 28173123
- Web of Science ID : WOS:000395809100010