Mutational analysis of the Jagged 1 gene in Alagille syndrome families
| Autor: | Teruaki Suzuki, Takeshi Ikegaya, Noboru Kobayashi, Sachiko Okano, Jun Abe, Zeng-Rong Yuan, Takao Kohsaka, Masao Yamada |
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| Rok vydání: | 1998 |
| Předmět: |
Male
JAG1 RNA Splicing Nonsense mutation Biology medicine.disease_cause Frameshift mutation Exon Alagille syndrome Genetics medicine Humans Point Mutation Serrate-Jagged Proteins Frameshift Mutation Molecular Biology Genetics (clinical) Polymorphism Single-Stranded Conformational DNA Primers Genes Dominant Mutation Splice site mutation Base Sequence Calcium-Binding Proteins Autosomal dominant trait Membrane Proteins Proteins General Medicine DNA medicine.disease Molecular biology Pedigree Alagille Syndrome Codon Nonsense Intercellular Signaling Peptides and Proteins Female Gene Deletion Jagged-1 Protein |
| Zdroj: | Human molecular genetics. 7(9) |
| ISSN: | 0964-6906 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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