FERMT1 promoter mutations in patients with Kindler syndrome. (7th October 2014)

• Record Type: Journal Article
• Authors: Has, C.; Chmel, N.; Levati, L.; Neri, I.; Sonnenwald, T.; Pigors, M.; Godbole, K.; Dudhbhate, A.; Bruckner‐Tuderman, L.; Zambruno, G.; Castiglia, D.
• Is Part Of: Clinical genetics. Volume 88:Number 3(2015:Sep.)
• Page Start: 248
• Page End: 254
• Publication Date: 2014-10-07
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12490
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12490-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12490-para-0001">Mutations in the <italic>FERMT1</italic> gene, encoding the focal adhesion protein kindlin‐1 underlie the Kindler syndrome (KS), an autosomal recessive skin disorder with a phenotype comprising skin blistering, photosensitivity, progressive poikiloderma with extensive skin atrophy, and propensity to skin cancer. The <italic>FERMT1</italic> mutational spectrum comprises gross genomic deletions, splice site, nonsense, and frameshift mutations, which are scattered over the coding region spanning exon 2–15. We now report three KS families with mutations affecting the promoter region of <italic>FERMT1</italic>. Two of these mutations are large deletions (∼38.0 and 1.9 kb in size) and one is a single nucleotide variant (c.‐20A&gt;G) within the 5′ untranslated region (UTR). Each mutation resulted in loss of gene expression in patient skin or cultured keratinocytes. Reporter assays showed the functional relevance of the genomic regions deleted in our patients for <italic>FERMT1</italic> gene transcription and proved the causal role of the c.‐20A&gt;G variant in reducing transcriptional activity.</p> </abstract>