Balanced Translocation Disrupting JAG1 Identified by Optical Genomic Mapping in Suspected Alagille Syndrome

We report the clinical and genetic features of a Han Chinese boy who presented with disease suspect for Alagille syndrome (ALGS). Multiple genetic analyses (panel sequencing, multiplex-ligation-dependent probe amplification, and whole genome sequencing) failed to uncover a causative variant. Optical...

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Published in:Human mutation 2023-06, Vol.2023, p.1-7
Main Authors: Zhang, Yi-Qiong, Gao, Peng-Fei, Yang, Jing-Min, Zhang, Jing, Lu, Yu-Lan, Wang, Jian-She
Format: Article
Language:English
Subjects:
Alagille syndrome
Biomarkers
Breakpoints
Chromosomes
Creatinine
Gallbladder diseases
Gene mapping
Genetic analysis
Genetic counseling
Genetic testing
Genomes
Genomics
Labeling
Pulmonary arteries
Whole genome sequencing
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creator Zhang, Yi-Qiong
Gao, Peng-Fei
Yang, Jing-Min
Zhang, Jing
Lu, Yu-Lan
Wang, Jian-She
description We report the clinical and genetic features of a Han Chinese boy who presented with disease suspect for Alagille syndrome (ALGS). Multiple genetic analyses (panel sequencing, multiplex-ligation-dependent probe amplification, and whole genome sequencing) failed to uncover a causative variant. Optical genomic mapping detected a reciprocal translocation between chromosomes 4 and 20, interrupting JAG1. Long-range polymerase chain reaction and targeted sequencing identified the exact breakpoints. Sanger sequencing and reanalysis of genome sequencing raw data further confirmed the result. This translocation is expected to generate aberrant JAG1 transcripts that lead to complete loss of JAG1 expression. This is the first t(4;20)(q22.1;p12.2) balanced translocation detected by optical genomic mapping and characterized at base-pair resolution in ALGS. Our approach permitted precise diagnosis and genetic counseling.
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subjects Alagille syndrome
Biomarkers
Breakpoints
Chromosomes
Creatinine
Gallbladder diseases
Gene mapping
Genetic analysis
Genetic counseling
Genetic testing
Genomes
Genomics
Labeling
Pulmonary arteries
Whole genome sequencing
title Balanced Translocation Disrupting JAG1 Identified by Optical Genomic Mapping in Suspected Alagille Syndrome
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