2. Academic Validation
  3. Mutations in SDR9C7 gene encoding an enzyme for vitamin A metabolism underlie autosomal recessive congenital ichthyosis

Mutations in SDR9C7 gene encoding an enzyme for vitamin A metabolism underlie autosomal recessive congenital ichthyosis

  • Hum Mol Genet. 2016 Oct 15;25(20):4484-4493. doi: 10.1093/hmg/ddw277.
Yohya Shigehara 1,  Shujiro Okuda 2,  Georges Nemer 3,  Adele Chedraoui 4,  Ryota Hayashi 1,  Fadi Bitar 5,  Hiroyuki Nakai 6,  Ossama Abbas 7,  Laetitia Daou 8,  Riichiro Abe 1,  Maria Bou Sleiman 7,  Abdul Ghani Kibbi 7,  Mazen Kurban 3 7 9,  Yutaka Shimomura 1
Affiliations

Affiliations

  • 1 Divisions of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
  • 2 Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
  • 3 Biochemistry & molecular genetics, American University of Beirut Medical Center, Beirut, Lebanon.
  • 4 Department of Dermatology, Lebanese American University-Hospital Rizk, Beirut, Lebanon.
  • 5 Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon.
  • 6 Faculty of Agriculture, Niigata University, Niigata, Japan.
  • 7 Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon.
  • 8 Department of Laboratory medicine, American University of Beirut Medical Center, Beirut, Lebanon.
  • 9 Department of Dermatology, Columbia University, New York, NY, USA
PMID: 28173123 DOI: 10.1093/hmg/ddw277
Abstract

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 9.47 Mb 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 metabolism in terminal differentiation of the epidermis in humans.

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