Elsevier

Genomics

Volume 25, Issue 1, 1 January 1995, Pages 192-198
Genomics

Cloning of the β3 chain gene (LAMB3) of human laminin 5, a candidate gene in junctional epidermolysis bullosa

https://doi.org/10.1016/0888-7543(95)80125-6Get rights and content

Abstract

Laminin 5 consists of three polypeptides, α3, β3, and γ2, encoded by the genes LAMA3, LAMB3, and LAMC2, respectively. In this study, we have elucidated the exon—intron organization of the human LAMB3 gene. Characterization of five overlapping λ phage DNA clones revealed that the gene was approximately 29 kb in size. Subsequent sequence data revealed that the gene consisted of 23 exons that varied from 64 to 379 bp in size, accounting for the full-length cDNA with an open reading frame of 3516 bp encoding 1172 amino acids. Comparison of the LAMB3 gene structure with the previously characterized LAMB1 gene revealed that LAMB3 was considerably more compact. Knowledge of the exon—intron organization of the LAMB3 gene will facilitate elucidation of mutations in patients with the junctional forms of epidermolysis bullosa, some of which have been associated with mutations in the laminin 5 genes.

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      COL7A1 markers were subsequently used to map the recessive form of dystrophic epidermolysis bullosa to the same locus (Hovnanian et al., 1992), and causative mutations in COL7A1 for recessive (Christiano et al., 1993) and dominant (Christiano et al., 1994) dystrophic epidermolysis bullosa were published in the following 2 years. Only a few months later, and with the same candidate gene approach and rapid pace that surprisingly put pathogenesis reports ahead of those describing a gene’s cloning and characterization, recessive junctional epidermolysis bullosa was found to be caused by mutations in the genes encoding the three subunit polypeptides of laminin-5 (LAMA3 [Kivirikko et al., 1995], LAMB3 [Pulkkinen et al., 1994b, 1995], and LAMC2 [Aberdam et al., 1994; Pulkkinen et al., 1994a]) and the collagen gene COL17A1 (McGrath et al., 1995). Mutations in LAMB3 account for most junctional epidermolysis bullosa cases, because of the prevalence of two nonsense mutations that arise recurrently within mutational hotspots (Kivirikko et al., 1996).

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    This study was supported by USPHS/NIH Grants P01-AR38923 and T32-07561 and by the Dermatology Foundation. Sequence data from this article have been deposited in GenBank under Accession Nos. U17744–U17760.

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