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: J A McGrath, S Kivirikko, S Ciatti, C Moss, A M Christiano, J Uitto
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 106 Issue 4 Pg. 781-4 (Apr 1996) ISSN: 0022-202X [Print] United States
• PMID: 8618022 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Laminin

Topics

• Base Sequence
• Epidermolysis Bullosa, Junctional (etiology, genetics)
• Haplotypes
• Humans
• Infant
• Laminin (genetics)
• Male
• Molecular Sequence Data
• Mutation
• Pakistan (ethnology)
• Polymorphism, Genetic