Recurrent mutations in kindlin-1, a novel keratinocyte focal contact protein, in the autosomal recessive skin fragility and photosensitivity disorder, Kindler syndrome.

[kindler syndrome]

Kindler syndrome (OMIM 173650 ) is a rare autosomal recessive disorder characterized by trauma-induced blister formation (especially in childhood ) and photosensitivity . Other features include mucocutaneous scarring and progressive poikiloderma . There is also an increased risk of skin and mucous membrane malignancy . The disorder was recently mapped to 20 p 12 .3 and pathogenic mutations were identified in a new gene , KIND 1 . This gene encodes a 677 amino acid protein , kindlin-1 , a component of focal contacts in keratinocytes . In this study , we identified four new recurrent mutations in KIND 1 in 16 individuals with Kindler syndrome from 13 families of Pakistani (676 insC ), UK Caucasian (E 304 X ), Omani (W 616 X ), or Italian (958 -1 G > A ) origins . Haplotype analysis demonstrated common ancestral mutant alleles for each mutation , apart from one of the six Pakistani families in which the mutation 676 insC (which occurs in a repeat of seven cytosines ) was present on a different genetic background . All mutations were homozygous , apart from the three UK Caucasian cases that were all compound heterozygotes (second allele mutations : L 302 X , 1161 delA , 1909 delA ). All mutations were associated with markedly reduced or absent skin immunostaining with an antikindlin-1 antibody . These loss -of-function KIND 1 mutations demonstrate the importance of kindlin-1 in maintaining epithelial integrity , although the mechanism linking this mutant protein to photosensitivity and poikiloderma remains to be determined . Delineation of these recurrent mutations is also relevant to optimizing mutation detection strategies in Kindler syndrome patients from particular ethnic backgrounds .

Diseases
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Diseases presenting "increased risk of skin and mucous membrane malignancy" symptom

kindler syndrome

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