Novel mutations in the LAMB3 gene shared by two Japanese unrelated families with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing

Y. Takizawa, H. Shimizu, L. Pulkkinen, Y. Hiraoka, J. A. McGrath, K. Suzumori, S. Aiso, J. Uitto, T. Nishikawa

研究成果: Article

21 引用 (Scopus)

抜粋

The LAMB3 gene encoding the β3 chain of laminin 5 is a candidate gene for mutations in the autosomal recessive blistering skin disorder, junctional epidermolysis bullosa. In this study, we performed genetic analyses in two unrelated Japanese families with Herlitz junctional epidermolysis bullosa and identified two novel nonsense mutations in the LAMB3 gene. One of them, Q166X (CAG → TAG), was found in the maternal allele of family 1 and the paternal allele of family 2. Conversely, the other mutations, W610X (TGG → TGA), was found in the paternal allele of family 1 and the maternal allele of family 2. Thus, probands of both families were compound heterozygotes for these nonsense mutations. Haplotype analyses with intragenic LAMB3 polymorphisms suggested that both mutations had arisen independently in these two families. Both mutations create a premature translation termination codon predicting truncated β3 chains that lead to absent expression of laminin 5 in the epidermal basement membrane zone. Based on these results, DNA-based prenatal diagnosis was performed by chorionic villus sampling for subsequent pregnancies in both families. Both fetuses were found to be heterozygous carriers of the W610X mutation together with a normal LAMB3 allele, indicating that they were phenotypically unaffected. These findings expand the repertoire of LAMB3 mutations in junctional epidermolysis bullosa, and emphasize the notion that premature termination codons in both alleles of the laminin 5 genes result in Herlitz junctional epidermolysis bullosa.

元の言語English
ページ(範囲)174-178
ページ数5
ジャーナルJournal of Investigative Dermatology
110
発行部数2
DOI
出版物ステータスPublished - 1998
外部発表Yes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

フィンガープリント Novel mutations in the LAMB3 gene shared by two Japanese unrelated families with Herlitz junctional epidermolysis bullosa, and their application for prenatal testing' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用