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Mutations in SMARCAD 1 cause autosomal dominant adermatoglyphia and perturb the expression of epidermal differentiation‐associated genes
Author(s) -
Nousbeck J.,
Sarig O.,
Magal L.,
Warshauer E.,
Burger B.,
Itin P.,
Sprecher E.
Publication year - 2014
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/bjd.13176
Subject(s) - biology , haploinsufficiency , genetics , gene , exon , gene isoform , phenotype , transcription factor , mutation , subfamily , microbiology and biotechnology
Summary Background Autosomal dominant adermatoglyphia ( ADG ) is characterized by lack of palmoplantar epidermal ridges. Recently, ADG was found to be caused in one family by a mutation in SMARCAD 1 , a member of the SNF subfamily of the helicase protein superfamily. Objectives To investigate the genetic basis of ADG . Methods We used direct sequencing and global gene expression analysis. Results We identified three novel heterozygous mutations in SMARCAD 1 (c.378 + 2T > C, c.378 + 5G > C and c.378 + 1G > A) in a total of six patients. Surprisingly, all four ADG ‐causing mutations identified to date disrupt a single conserved donor splice site adjacent to the 3′ end of a noncoding exon and are predicted to result in haploinsufficiency for a skin‐specific isoform of SMARCAD 1 . These data indicate a pivotal role for the SMARCAD 1 ‐skin specific isoform in dermatoglyph formation. In order to better understand the consequences of ADG ‐associated mutations, we ascertained the global transcription profiles of primary keratinocytes downregulated for SMARCAD 1 and of patient‐derived keratinocytes. A total of eight genes were found to be differentially expressed in both patient‐derived and knocked down keratinocytes. Of interest, these differentially expressed genes have been implicated in epidermal ontogenesis and differentiation, and in psoriasis, which is characterized by abnormal finger ridge patterns. Conclusions The present data suggest that ADG is genetically homogeneous and result from perturbed expression of epidermal differentiation‐associated genes.