| Autor: |
Shigehara Y; Divisions of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Okuda S; Division of Bioinformatics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Nemer G; Biochemistry & molecular genetics, American University of Beirut Medical Center, Beirut, Lebanon., Chedraoui A; Department of Dermatology, Lebanese American University-Hospital Rizk, Beirut, Lebanon., Hayashi R; Divisions of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Bitar F; Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon., Nakai H; Faculty of Agriculture, Niigata University, Niigata, Japan., Abbas O; Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon., Daou L; Department of Laboratory medicine, American University of Beirut Medical Center, Beirut, Lebanon., Abe R; Divisions of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan., Sleiman MB; Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon., Kibbi AG; Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon., Kurban M; Biochemistry & molecular genetics, American University of Beirut Medical Center, Beirut, Lebanon.; Department of Dermatology, American University of Beirut Medical Center, Beirut, Lebanon.; Department of Dermatology, Columbia University, New York, NY, USA, Shimomura Y; Divisions of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. |
| Abstrakt: |
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. |
