Journal Article

Mutational Analysis of the <i>Jagged 1</i> Gene in Alagille Syndrome Families

Zeng-Rong Yuan, Takao Kohsaka, Takeshi Ikegaya, Teruaki Suzuki, Sachiko Okano, Jun Abe, Noboru Kobayashi and Masao Yamada

in Human Molecular Genetics

Volume 7, issue 9, pages 1363-1369
Published in print September 1998 | ISSN: 0964-6906
Published online September 1998 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/7.9.1363
Mutational Analysis of the Jagged 1 Gene in Alagille Syndrome Families

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Alagille syndrome (AGS) is an autosomal dominant disease characterized by five major abnormalities in the liver, heart, face, vertebrae and eye. The responsible gene has been recently identified as the human Jagged 1 (JAG1) gene, which encodes a ligand for the Notch receptor. We analyzed the JAG1 gene in eight AGS families, including affected and unaffected individuals, at the genomic DNA level, mainly by single-strand conformational polymorphism (SSCP) and DNA sequencing analysis. Four categories of mutations were identified: (i) four frameshift mutations in exons 9, 22, 24 and 26 were exhibited respectively in affected individuals of four AGS families, which resulted in moving the translational frame of JAG1; (ii) one nonsense mutation, a 1 bp substitution in exon 5 of the EGF-like repeat domain, was detected in two unrelated AGS families, which altered codon 235 from arginine to stop; (iii) one acceptor splice site mutation of exon 5 was revealed in a sporadic patient; and (iv) a 1.3 Mb deletion, which included the entire JAG1 gene, was found in another patient. Our results further demonstrate that AGS is a dominant disease and suggest that the JAG1 gene exerts a fundamental role in regulating genes involved in development.

Journal Article.  4513 words.  Illustrated.

Subjects: Genetics and Genomics

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