New intragenic and promoter region deletion mutations in FERMT1 underscore genetic homogeneity in Kindler syndrome. (April 2014)

• Record Type: Journal Article
• Authors: Fuchs‐Telem, D.; Nousbeck, J.; Singer, A.; McGrath, J. A.; Sarig, O.; Sprecher, E.
• Is Part Of: Clinical and experimental dermatology. Volume 39:Number 3(2014)
• Page Start: 361
• Page End: 367
• Publication Date: 2014-04
• Subjects: Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/ced.12222
• Languages: English
• ISSNs: 0307-6938

Abstract

<abstract abstract-type="main" id="ced12222-abs-0001"> <title>Summary</title> <sec id="ced12222-sec-0001" sec-type="section"> <title>Background</title> <p>Kindler syndrome (KS) is a rare autosomal recessive skin disorder, which was recently reclassified as a subtype of epidermolysis bullosa. Despite the fact that loss‐of‐function mutations in the <italic>FERMT1</italic> gene, encoding kindlin‐1, have been shown to cause the syndrome in numerous patients, a small number of typical cases of KS in which <italic>FERMT1</italic> mutations could not be identified has raised the possibility that the disorder may be genetically heterogeneous.</p> </sec> <sec id="ced12222-sec-0002" sec-type="section"> <title>Aim</title> <p>To assess two highly consanguineous families with clinical characteristics of KS.</p> </sec> <sec id="ced12222-sec-0003" sec-type="section"> <title>Results</title> <p>In the first family, a hitherto unreported deletion (c.137–140delTAGT) in <italic>FERMT1</italic> was detected, which is predicted to lead to premature termination of translation. However, direct sequencing of the coding region of <italic>FERMT1</italic> failed to disclose any pathogenic change in the second family. To confirm the possibility that the disease in this family may be due to a mutation in another gene, we used homozygosity mapping, and found that all affected family members share a segment of homozygosity on 20p12.3, spanning the <italic>FERMT1</italic> gene. Accordingly, a large and highly unusual deletion (g.‐711‐1241del) spanning the putative <italic>FERMT1</italic> promoter sequence and the first noncoding exon of the gene was found to cosegregate with the disease phenotype in this family, and to prevent transcription of the gene, as attested by the lack of <italic>FERMT1</italic> message in the skin of a patient.</p> </sec> <sec id="ced12222-sec-0004" sec-type="section"> <title>Conclusion</title> <p>The present data provide evidence in support of genetic homogeneity in KS.</p> </sec> </abstract>