Alagille syndrome

A new missense mutation detected by whole-exome sequencing in a case previously found to be negative by DHPLC and MLPA

Diego Vozzi, D. Licastro, S. Martelossi, E. Athanasakis, P. Gasparini, A. Fabretto

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Alagille syndrome (ALGS, MIM 118450) is an autosomal dominant, multisystem disorder with high variability. Two genes have been described: JAG1 and NOTCH2. The population prevalence is 1:70,000 based on the presence of neonatal liver disease. The majority of cases (∼97%) are caused by haploinsufficiency of the JAG1 gene on 20p11.2p12, either due to mutations or deletions at the locus. Less than 1% of cases are caused by mutations in NOTCH2. The most widely used methods for mutational screening include denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Very recently, whole-exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new opportunities for mutations/genes identification. A proband and its family, negative for the presence of mutations in JAG1 and NOTCH2 genes by neither DHPLC nor MLPA, were analyzed by WES. A missense mutation, not previously described, in JAG1 gene was identified. This result shows an improvement in the mutation detection rate due to novel sequencing technology suggesting the strong need to reanalyze all negative cases.

Original languageEnglish
Pages (from-to)207-210
Number of pages4
JournalMolecular Syndromology
Volume4
Issue number4
DOIs
Publication statusPublished - Apr 2013
Externally publishedYes

Fingerprint

Alagille Syndrome
Exome
Multiplex Polymerase Chain Reaction
Missense Mutation
High Pressure Liquid Chromatography
Genes
Mutation
Infant, Newborn, Diseases
Technology
Haploinsufficiency
Sequence Deletion
Mutation Rate
Liver Diseases
Population

Keywords

  • Alagille syndrome
  • JAG1
  • Whole-exome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Alagille syndrome : A new missense mutation detected by whole-exome sequencing in a case previously found to be negative by DHPLC and MLPA. / Vozzi, Diego; Licastro, D.; Martelossi, S.; Athanasakis, E.; Gasparini, P.; Fabretto, A.

In: Molecular Syndromology, Vol. 4, No. 4, 04.2013, p. 207-210.

Research output: Contribution to journalArticle

Vozzi, Diego ; Licastro, D. ; Martelossi, S. ; Athanasakis, E. ; Gasparini, P. ; Fabretto, A. / Alagille syndrome : A new missense mutation detected by whole-exome sequencing in a case previously found to be negative by DHPLC and MLPA. In: Molecular Syndromology. 2013 ; Vol. 4, No. 4. pp. 207-210.
@article{2ccc781754374d90922f8faf967b1007,
title = "Alagille syndrome: A new missense mutation detected by whole-exome sequencing in a case previously found to be negative by DHPLC and MLPA",
abstract = "Alagille syndrome (ALGS, MIM 118450) is an autosomal dominant, multisystem disorder with high variability. Two genes have been described: JAG1 and NOTCH2. The population prevalence is 1:70,000 based on the presence of neonatal liver disease. The majority of cases (∼97{\%}) are caused by haploinsufficiency of the JAG1 gene on 20p11.2p12, either due to mutations or deletions at the locus. Less than 1{\%} of cases are caused by mutations in NOTCH2. The most widely used methods for mutational screening include denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Very recently, whole-exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new opportunities for mutations/genes identification. A proband and its family, negative for the presence of mutations in JAG1 and NOTCH2 genes by neither DHPLC nor MLPA, were analyzed by WES. A missense mutation, not previously described, in JAG1 gene was identified. This result shows an improvement in the mutation detection rate due to novel sequencing technology suggesting the strong need to reanalyze all negative cases.",
keywords = "Alagille syndrome, JAG1, Whole-exome sequencing",
author = "Diego Vozzi and D. Licastro and S. Martelossi and E. Athanasakis and P. Gasparini and A. Fabretto",
year = "2013",
month = "4",
doi = "10.1159/000347231",
language = "English",
volume = "4",
pages = "207--210",
journal = "Molecular Syndromology",
issn = "1661-8769",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Alagille syndrome

T2 - A new missense mutation detected by whole-exome sequencing in a case previously found to be negative by DHPLC and MLPA

AU - Vozzi, Diego

AU - Licastro, D.

AU - Martelossi, S.

AU - Athanasakis, E.

AU - Gasparini, P.

AU - Fabretto, A.

PY - 2013/4

Y1 - 2013/4

N2 - Alagille syndrome (ALGS, MIM 118450) is an autosomal dominant, multisystem disorder with high variability. Two genes have been described: JAG1 and NOTCH2. The population prevalence is 1:70,000 based on the presence of neonatal liver disease. The majority of cases (∼97%) are caused by haploinsufficiency of the JAG1 gene on 20p11.2p12, either due to mutations or deletions at the locus. Less than 1% of cases are caused by mutations in NOTCH2. The most widely used methods for mutational screening include denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Very recently, whole-exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new opportunities for mutations/genes identification. A proband and its family, negative for the presence of mutations in JAG1 and NOTCH2 genes by neither DHPLC nor MLPA, were analyzed by WES. A missense mutation, not previously described, in JAG1 gene was identified. This result shows an improvement in the mutation detection rate due to novel sequencing technology suggesting the strong need to reanalyze all negative cases.

AB - Alagille syndrome (ALGS, MIM 118450) is an autosomal dominant, multisystem disorder with high variability. Two genes have been described: JAG1 and NOTCH2. The population prevalence is 1:70,000 based on the presence of neonatal liver disease. The majority of cases (∼97%) are caused by haploinsufficiency of the JAG1 gene on 20p11.2p12, either due to mutations or deletions at the locus. Less than 1% of cases are caused by mutations in NOTCH2. The most widely used methods for mutational screening include denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Very recently, whole-exome sequencing (WES) has become technically feasible due to the recent advances in next-generation sequencing technologies, therefore offering new opportunities for mutations/genes identification. A proband and its family, negative for the presence of mutations in JAG1 and NOTCH2 genes by neither DHPLC nor MLPA, were analyzed by WES. A missense mutation, not previously described, in JAG1 gene was identified. This result shows an improvement in the mutation detection rate due to novel sequencing technology suggesting the strong need to reanalyze all negative cases.

KW - Alagille syndrome

KW - JAG1

KW - Whole-exome sequencing

UR - http://www.scopus.com/inward/record.url?scp=84877297238&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877297238&partnerID=8YFLogxK

U2 - 10.1159/000347231

DO - 10.1159/000347231

M3 - Article

VL - 4

SP - 207

EP - 210

JO - Molecular Syndromology

JF - Molecular Syndromology

SN - 1661-8769

IS - 4

ER -