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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Mutations in CERS3 Cause Autosomal Recessive Congenital Ichthyosis in Humans
PLoS Genetics, Volume 9, No. 6, Article e1003536, Year 2013
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Description
Autosomal recessive congenital ichthyosis (ARCI) is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene deletion syndrome on chromosome 15q26.3. Genome-wide SNP-genotyping revealed a homozygous region in all affected individuals, including the same microdeletion that partially affects two coding genes (ADAMTS17, CERS3) and abolishes a sequence for a long non-coding RNA (FLJ42289). Whereas mutations in ADAMTS17 have recently been identified in autosomal recessive Weill-Marchesani-like syndrome in humans and dogs presenting with ophthalmologic, cardiac, and skeletal abnormalities, no disease associations have been described for CERS3 (ceramide synthase 3) and FLJ42289 so far. However, analysis of additional patients with non-syndromic ARCI revealed a splice site mutation in CERS3 indicating that a defect in ceramide synthesis is causative for the present skin phenotype of our patients. Functional analysis of patient skin and in vitro differentiated keratinocytes demonstrated that mutations in CERS3 lead to a disturbed sphingolipid profile with reduced levels of epidermis-specific very long-chain ceramides that interferes with epidermal differentiation. Taken together, these data present a novel pathway involved in ARCI development and, moreover, provide the first evidence that CERS3 plays an essential role in human sphingolipid metabolism for the maintenance of epidermal lipid homeostasis. © 2013 Radner et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3675029/bin/pgen.1003536.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3675029/bin/pgen.1003536.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3675029/bin/pgen.1003536.s003.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3675029/bin/pgen.1003536.s004.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3675029/bin/pgen.1003536.s005.doc
Authors & Co-Authors
Radner, Franz P.W.
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Marrakchi, Slaheddine
Tunisia, Sfax
Chu Hedi-chaker
Kirchmeier, Peter
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Germany, Freiburg Im Breisgau
Universität Freiburg
Kim, Gwangjin
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Germany, Freiburg Im Breisgau
Universität Freiburg
Ribierre, Florence
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
Kamoun, Bourane
Tunisia, Sfax
Chu Habib Bourguiba
Abid, L.
Tunisia, Sfax
Chu Hedi-chaker
Leipoldt, Michael
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Turki, Hamaida
Tunisia, Sfax
Chu Hedi-chaker
Schempp, Werner
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Heilig, Roland
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
Lathrop, Mark G.
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
France, Paris
Fondation Jean Dausset - Ceph
Canada, Montreal
Université Mcgill
Fischer, Judith
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
France, Gif-sur-yvette
Commissariat a L'energie Atomique et Aux Energies Alternatives
Statistics
Citations: 111
Authors: 13
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pgen.1003536
e-ISSN:
15537404
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Noncommunicable Diseases