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A novel mutation of keratin 9 in a large Chinese family with epidermolytic palmoplantar keratoderma
Author(s) -
He XH.,
Zhang XN.,
Mao W.,
Chen HP.,
Xu LR.,
Chen H.,
He XL.,
Le YP.
Publication year - 2004
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.0007-0963.2004.05865.x
Subject(s) - exon , keratin , biology , microbiology and biotechnology , keratin 6a , denaturing high performance liquid chromatography , genetics , mutation , palmoplantar keratoderma , gene mutation , gene , genomic dna , intermediate filament , cytoskeleton , cell
Summary Background Epidermolytic palmoplantar keratoderma (EPPK) is an autosomal dominant inherited skin disorder characterized by diffuse yellow thickening of the skin of the palms and soles, sharply bordered with erythematous margins. Histologically and ultrastructurally, EPPK presents cytolysis of keratinocytes and abnormal aggregation of tonofilaments in the suprabasal layers of the epidermis. To date, 15 different mutations of the keratin 9 gene ( KRT9 ) have been demonstrated to cause most cases of EPPK. Objectives To identify the KRT9 mutation in a large Chinese family with EPPK. Methods Denaturing high‐performance liquid chromatography (DHPLC), DNA sequencing and allele‐specific polymerase chain reaction (AS‐PCR) were used to screen exon 1 of the KRT9 gene for sequence variations. Results The DHPLC elution profiles of the DNA fragments amplified from the affected samples differed from those obtained from unaffected individuals, indicating that a sequence variation existed within the analysed fragment of KRT9 . DNA sequencing revealed a novel insertion–deletion mutation in the exon 1 of KRT9, 497delAinsGGCT, resulting in the change of tyrosine 166 to tryptophan and leucine (Y166delinsWL). AS‐PCR confirmed the mutation was not a common polymorphism. Conclusions The results suggest the molecular basis of EPPK in this Chinese family and provide further evidence that mutations in the helix initiation motif of keratin 9 underlie Chinese EPPK.