Unknown

Dataset Information

0

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

ABSTRACT: 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.

SUBMITTER: Cabral RM 

PROVIDER: S-EPMC4362535 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

Cabral Rita M RM   Kurban Mazen M   Wajid Muhammad M   Shimomura Yutaka Y   Petukhova Lynn L   Christiano Angela M AM  

Genomics 20120125 4

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 immunofluor  ...[more]

Similar Datasets

Unknown Proband Whole-Exome Sequencing Identified Genes Responsible for Autosomal Recessive Non-Syndromic Hearing Loss in 33 Chinese Nuclear Families.
| S-EPMC6650584 | biostudies-literature
Unknown Whole-exome sequencing efficiently detects rare mutations in autosomal recessive nonsyndromic hearing loss.
| S-EPMC3511533 | biostudies-literature
Unknown Homozygosity mapping and exome sequencing reveal GATAD1 mutation in autosomal recessive dilated cardiomyopathy.
| S-EPMC3248690 | biostudies-literature
Unknown Whole exome sequencing identifies a novel homozygous frameshift mutation in the ASPM gene, which causes microcephaly 5, primary, autosomal recessive.
| S-EPMC5770997 | biostudies-literature
Unknown Exome sequencing reveals a novel TTC19 mutation in an autosomal recessive spinocerebellar ataxia patient.
| S-EPMC3890717 | biostudies-literature
Unknown Whole exome sequencing reveals novel EYS mutations in Chinese patients with autosomal recessive retinitis pigmentosa.
| S-EPMC6363637 | biostudies-literature
Unknown Whole-exome sequencing revealed HKDC1 as a candidate gene associated with autosomal-recessive retinitis pigmentosa.
| S-EPMC6240732 | biostudies-literature
Unknown Identification of copy number variants through whole-exome sequencing in autosomal recessive nonsyndromic hearing loss.
| S-EPMC4150376 | biostudies-literature
Unknown Whole Exome Sequencing Confirms Molecular Diagnostics of Three Pakhtun Families With Autosomal Recessive Epidermolysis Bullosa.
| S-EPMC8369263 | biostudies-literature
Unknown Case Report: Whole exome sequencing reveals a novel frameshift deletion mutation p.G2254fs in COL7A1 associated with autosomal recessive dystrophic epidermolysis bullosa.
| S-EPMC4926754 | biostudies-literature