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A new homozygous nonsense mutation in LAMA 3A underlying laryngo‐onycho‐cutaneous syndrome
Author(s) -
Barzegar M.,
Mozafari N.,
Kariminejad A.,
Asadikani Z.,
Ozoemena L.,
McGrath J.A.
Publication year - 2013
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.12522
Subject(s) - nonsense mutation , exon , epidermolysis bullosa , nonsense , laminin , mutation , immunostaining , genetics , biology , poikiloderma , pathology , medicine , genodermatosis , gene , missense mutation , immunohistochemistry , extracellular matrix
Summary Laryngo‐onycho‐cutaneous ( LOC ) syndrome is a subtype of autosomal recessive junctional epidermolysis bullosa in which there is prominent skin and mucosal granulation tissue that can lead to delayed wound healing, laryngeal obstruction and blindness. Thus far, all cases are of Punjabi ancestry and have been shown to result from a founder mutation in the LAMA 3 gene, notably involving a single nucleotide insertion mutation in exon 39, which is specific to the LAMA 3A (designated exon 1 of LAMA 3A ) and not the LAMA 3B1 or LAMA 3B2 isoforms. Here, we describe a new pedigree with LOC syndrome. Affected individuals (from Iran) have the characteristic clinicopathological and molecular features of LOC syndrome: prominent granulation tissue (especially affecting the eyes), normal intensity laminin‐332 immunostaining at the dermal–epidermal junction, and autosomal recessive mutations in the LAMA 3A ‐specific exon. The pathogenic mutation is a homozygous nonsense mutation, designated p.Gln57X, which just affects the laminin‐α3a transcript. These findings therefore expand the molecular basis of LOC syndrome.