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A novel TGM 1 mutation, leading to multiple splicing rearrangements, is associated with autosomal recessive congenital ichthyosis
Author(s) -
OrtegaRecalde O.,
Moreno M. B.,
Vergara J. I.,
Fonseca D. J.,
Rojas R. F.,
Mosquera H.,
Medina C. L.,
Restrepo C. M.,
Laissue P.
Publication year - 2015
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.12627
Subject(s) - ichthyosis , congenital ichthyosis , lamellar ichthyosis , genetics , mutation , biology , exon , medicine , dermatology , gene
Summary Autosomal recessive congenital ichthyosis ( ARCI ) is a group of rare, clinically heterogeneous skin disorders that affect cornification. ARCI includes lamellar ichthyosis, congenital ichthyosiform erythroderma and harlequin ichthyosis. TGM 1 mutations cause > 50% of ARCI cases in the USA . We report two siblings with ARCI . They were found to carry a novel aetiological TGM 1 mutation, which leads to the synthesis of multiple abnormal transcripts. These molecules resulted from three independent mechanisms: intron retention, exon skipping and activation of expand cryptic splice sites. Taken together, our findings expand the known TGM 1 mutation repertoire, and provide an insight into the molecular mechanisms leading to ARCI phenotypes. These results could be useful for genetic counselling and future potential genotype–phenotype correlations.