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New intragenic and promoter region deletion mutations in FERMT 1 underscore genetic homogeneity in K indler syndrome
Author(s) -
FuchsTelem D.,
Nousbeck J.,
Singer A.,
McGrath J. A.,
Sarig O.,
Sprecher E.
Publication year - 2014
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/ced.12222
Subject(s) - genetics , biology , mutation , medicine , gene
Summary Background 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 FERMT 1 gene, encoding kindlin‐1, have been shown to cause the syndrome in numerous patients, a small number of typical cases of KS in which FERMT 1 mutations could not be identified has raised the possibility that the disorder may be genetically heterogeneous. Aim To assess two highly consanguineous families with clinical characteristics of KS . Results In the first family, a hitherto unreported deletion (c.137–140del TAGT ) in FERMT 1 was detected, which is predicted to lead to premature termination of translation. However, direct sequencing of the coding region of FERMT 1 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 FERMT 1 gene. Accordingly, a large and highly unusual deletion (g.‐711‐1241del) spanning the putative FERMT 1 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 FERMT 1 message in the skin of a patient. Conclusion The present data provide evidence in support of genetic homogeneity in KS .