title: A recurrent homozygous nonsense mutation within the LAMA3 gene as a cause of Herlitz junctional epidermolysis bullosa in patients of Pakistani ancestry: evidence for a founder effect.
abstract: The anchoring filament protein laminin 5 is abnormally expressed in the skin of patients with Herlitz junctional epidermolysis bullosa (H-JEB). In this study, we performed mutational analysis on genomic DNA from a H-JEB child of first-cousin Pakistani parents, and identified a homozygous C-to-T transition in the LAMA3 gene of laminin 5 resulting in a premature termination codon (CGA-TGA) on both alleles. This mutation, R650X, has been previously reported in two other seemingly unrelated H-JEB individuals of Pakistani ancestry. Although this mutation may represent a mutational hotspot within the LAMA3 gene, haplotype analysis based on a silent intragenic polymorphism (GCC/GCG, alanine 429; GenBank no. L34155), and on three flanking microsatellite polymorphism (D18S45, D18S478, and D18S480), suggests that a common ancestral allele may be present in all three cases.
authors.affiliation: Department of Dermatolgy, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: McGrath
authors.forename: S
authors.initials: S
authors.lastname: Kivirikko
authors.forename: S
authors.initials: S
authors.lastname: Ciatti
authors.forename: C
authors.initials: C
authors.lastname: Moss
authors.forename: A M
authors.initials: AM
authors.lastname: Christiano
authors.forename: J
authors.initials: J
authors.lastname: Uitto
mesh_terms: D001483:Base Sequence; D016109:Epidermolysis Bullosa, Junctional / Q000209:etiology / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007797:Laminin / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010154:Pakistan / Q000208:ethnology; D011110:Polymorphism, Genetic
chemical_list: D007797:Laminin