Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome

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• 作者：Rita M. Cabral^a ; ¹ ; Mazen Kurban^a ; ¹ ; Muhammad Wajid^a ; Yutaka Shimomura^a ; Lynn Petukhova^a ; ^b ; Angela M. Christiano^a ; ^c ; ^{amc65@columbia.edu}
• 关键词：GalNAc4-ST ; N-acetylgalactosamine-4-O-sulfotransferase ; PSS ; peeling skin syndrome ; APSS ; acral peeling skin syndrome ; GAG ; glycosaminoglycan ; TGM5 ; tranglutaminase 5 ; CDSN ; corneodesmosin ; NS ; Netherton syndrome ; CSTA ; cystatin A ; DMMB ; 1 ; 9-dimethylmethy
• 刊名：Genomics
• 出版年：2012
• 期刊代码：170_08887543
• 类别：bio
• 出版时间：April, 2012
• 卷：99
• 期：4
• 页码：202-208
• 文件大小：1263 K

摘要

Generalized peeling skin syndrome (PSS) is an autosomal recessive genodermatosis characterized by lifelong, continuous shedding of the upper epidermis. Using whole-genome homozygozity mapping and whole-exome sequencing, we identified a novel homozygous missense mutation (c.229C>T, R77W) within the CHST8 gene, in a large consanguineous family with non-inflammatory PSS type A. CHST8 encodes a Golgi transmembrane N-acetylgalactosamine-4-O-sulfotransferase (GalNAc4-ST1), which we show by immunofluorescence staining to be expressed throughout normal epidermis. A colorimetric assay for total sulfated glycosaminoglycan (GAG) quantification, comparing human keratinocytes (CCD1106 KERTr) expressing wild type and mutant recombinant GalNAc4-ST1, revealed decreased levels of total sulfated GAGs in cells expressing mutant GalNAc4-ST1, suggesting loss of function. Western blotting revealed lower expression levels of mutant recombinant GalNAc4-ST1 compared to wild type, suggesting that accelerated degradation may result in loss of function, leading to PSS type A. This is the first report describing a mutation as the cause of PSS type A.