TY - JOUR
T1 - Alagille syndrome
T2 - understanding the genotype-phenotype relationship and its potential therapeutic impact
AU - Halma, Jennifer
AU - Lin, Henry C.
N1 - Publisher Copyright:
© 2023 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2023
Y1 - 2023
N2 - Introduction: Alagille syndrome (ALGS) is an autosomal dominant, multisystem genetic disorder with wide phenotypic variability caused by mutations in the Notch signaling pathway, specifically from mutations in either the Jagged1 (JAG1) or NOTCH2 gene. The range of clinical features in ALGS can involve various organ systems including the liver, heart, eyes, skeleton, kidney, and vasculature. Despite the genetic mutations being well-defined, there is variable expressivity and individuals with the same mutation may have different clinical phenotypes. Areas covered: While no clear genotype-phenotype correlation has been identified in ALGS, this review will summarize what is currently known about the genotype-phenotype relationship and how this relationship influences the treatment of the multisystemic disorder. This review includes discussion of numerous studies which have focused on describing the genotype-phenotype relationship of different organ systems in ALGS as well as relevant basic science and population studies of ALGS. A thorough literature search was completed via the PubMed and National Library of Medicine GeneReviews databases including dates from 1969, when ALGS was first identified, to February 2023. Expert opinion: The genetics of ALGS are well defined; however, ongoing investigation to identify genotype-phenotype relationships as well as genetic modifiers as potential therapeutic targets is needed. Clinicians and patients alike would benefit from identification of a correlation to aid in diagnostic evaluation and management.
AB - Introduction: Alagille syndrome (ALGS) is an autosomal dominant, multisystem genetic disorder with wide phenotypic variability caused by mutations in the Notch signaling pathway, specifically from mutations in either the Jagged1 (JAG1) or NOTCH2 gene. The range of clinical features in ALGS can involve various organ systems including the liver, heart, eyes, skeleton, kidney, and vasculature. Despite the genetic mutations being well-defined, there is variable expressivity and individuals with the same mutation may have different clinical phenotypes. Areas covered: While no clear genotype-phenotype correlation has been identified in ALGS, this review will summarize what is currently known about the genotype-phenotype relationship and how this relationship influences the treatment of the multisystemic disorder. This review includes discussion of numerous studies which have focused on describing the genotype-phenotype relationship of different organ systems in ALGS as well as relevant basic science and population studies of ALGS. A thorough literature search was completed via the PubMed and National Library of Medicine GeneReviews databases including dates from 1969, when ALGS was first identified, to February 2023. Expert opinion: The genetics of ALGS are well defined; however, ongoing investigation to identify genotype-phenotype relationships as well as genetic modifiers as potential therapeutic targets is needed. Clinicians and patients alike would benefit from identification of a correlation to aid in diagnostic evaluation and management.
KW - Alagille syndrome
KW - JAG1
KW - NOTCH2
KW - genotype phenotype correlation
KW - liver disease
KW - pediatrics
UR - http://www.scopus.com/inward/record.url?scp=85169827938&partnerID=8YFLogxK
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U2 - 10.1080/17474124.2023.2255518
DO - 10.1080/17474124.2023.2255518
M3 - Review article
C2 - 37668532
AN - SCOPUS:85169827938
SN - 1747-4124
VL - 17
SP - 883
EP - 892
JO - Expert Review of Gastroenterology and Hepatology
JF - Expert Review of Gastroenterology and Hepatology
IS - 9
ER -