title: A novel TGM1 mutation, leading to multiple splicing rearrangements, is associated with autosomal recessive congenital ichthyosis.
abstract: 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. TGM1 mutations cause > 50% of ARCI cases in the USA. We report two siblings with ARCI. They were found to carry a novel aetiological TGM1 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 TGM1 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.
authors.affiliation: Genetics Unit, GENIUROS Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
authors.forename: O
authors.initials: O
authors.lastname: Ortega-Recalde
authors.affiliation: Genetics Unit, GENIUROS Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.
authors.forename: M B
authors.initials: MB
authors.lastname: Moreno
authors.affiliation: Department of Dermatology, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia.|Dermatology Unit, Clínica Carlos Ardila Lulle, Bucaramanga, Colombia.
authors.forename: J I
authors.initials: JI
authors.lastname: Vergara
authors.affiliation: Genetics Unit, GENIUROS Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.|Department of Molecular Genetics, Genética Molecular de Colombia, Bogotá, Colombia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Fonseca
authors.affiliation: Department of Dermatology, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia.|Dermatology Unit, Clínica Carlos Ardila Lulle, Bucaramanga, Colombia.
authors.forename: R F
authors.initials: RF
authors.lastname: Rojas
authors.affiliation: Department of Dermatology, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia.|Dermatology Unit, Clínica Carlos Ardila Lulle, Bucaramanga, Colombia.
authors.forename: H
authors.initials: H
authors.lastname: Mosquera
authors.affiliation: Department of Dermatology, Universidad Autónoma de Bucaramanga, Bucaramanga, Colombia.|Dermatology Unit, Clínica Carlos Ardila Lulle, Bucaramanga, Colombia.
authors.forename: C L
authors.initials: CL
authors.lastname: Medina
authors.affiliation: Genetics Unit, GENIUROS Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.|Department of Molecular Genetics, Genética Molecular de Colombia, Bogotá, Colombia.
authors.forename: C M
authors.initials: CM
authors.lastname: Restrepo
authors.affiliation: Genetics Unit, GENIUROS Group, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia.|Department of Molecular Genetics, Genética Molecular de Colombia, Bogotá, Colombia.
authors.forename: P
authors.initials: P
authors.lastname: Laissue
mesh_terms: D000328:Adult; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D006801:Humans; D016113:Ichthyosiform Erythroderma, Congenital / Q000235:genetics*; D009154:Mutation; D022821:RNA Splice Sites / Q000235:genetics*; D011503:Transglutaminases / Q000235:genetics*
chemical_list: D022821:RNA Splice Sites; D011503:Transglutaminases; C105804:transglutaminase 1