Jagged1 (JAG1) mutations in Alagille syndrome: increasing the mutation detection rate

Authors

  • DM Warthen,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • EC Moore,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • BM Kamath,

    1. Division of Gastroenterology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • JJD Morrissette,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • P Sanchez,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • DA Piccoli,

    1. Division of Gastroenterology and Nutrition, Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • ID Krantz,

    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • NB Spinner

    Corresponding author
    1. Division of Human Genetics and Molecular Biology, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    2. Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
    • Division of Human Genetics and Molecular Biology, 1007A Abramson Research Center, 3615 Civic Center Boulevard, The Children's Hospital of Philadelphia, Philadelphia, PA 19104
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Errata

This article is corrected by:

  1. Errata: Jagged1 (JAG1) Mutations in Alagille Syndrome: Increasing the Mutation Detection Rate Volume 34, Issue 2, 408, Article first published online: 20 December 2012

  • Communicated by Mireille Claustres

  • This article is a US Government work aid, and, as such, is in the public domain in the United States of America.

Abstract

Alagille syndrome (AGS) is caused by heterozygous mutations in JAG1, and mutations have been previously reported in about 70% of patients who meet clinical diagnostic criteria. We studied a cohort of 247 clinically well-defined patients, and using an aggressive and sequential screening approach we identified JAG1 mutations in 94% of individuals. Mutations were found in 232 out of 247 patients studied and 83 of the mutations were novel. This increase in the mutation rate was accomplished by combining rigorous clinical phenotyping, with a combination of mutation detection techniques, including fluorescence in situ hybridization (FISH), genomic and cDNA sequencing, and quantitative PCR. This higher rate of mutation identification has implications for clinical practice, facilitating genetic counseling, prenatal diagnosis, and evaluation of living-related liver transplant donors. Our results suggest that more aggressive screening may similarly increase the rate of mutation detection in other dominant and recessive disorders. Hum Mutat 27(5):436–443, 2006. Published 2006 Wiley-Liss, Inc.

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