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Open Access 01-12-2019 | Research

Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations

Authors: Qian Jiang, Yang Wang, Qi Li, Zhen Zhang, Ping Xiao, Hui Wang, Na Liu, Jian Wu, Feng Zhang, Aravinda Chakravarti, Wei Cai, Long Li

Published in: Orphanet Journal of Rare Diseases | Issue 1/2019

Abstract

Background

Hirschsprung disease (HSCR) is an inherited congenital disorder characterized by the absence of enteric ganglia in the distal part of the gut. RET is the major causative gene and contains > 80% of all known disease-causing mutations.

Results

To determine the incidence of RET pathogenic variants, be they Mendelian inherited, mosaic in parents or true de novo variants (DNVs) in 117 Chinese families, we used high-coverage NGS and droplet digital polymerase chain reaction (ddPCR) to identify 15 (12.8%) unique RET coding variants (7 are novel); one was inherited from a heterozygous unaffected mother, 11 were DNVs (73.3%), and 3 full heterozygotes were inherited from parental mosaicism (2 paternal, 1 maternal): two clinically unaffected parents were identified by NGS and confirmed by ddPCR, with mutant allele frequency (13–27%) that was the highest in hair, lowest in urine and similar in blood and saliva. An extremely low-level paternal mosaicism (0.03%) was detected by ddPCR in blood. Six positive-controls were examined to compare the mosaicism detection limit and sensitivity of NGS, amplicon-based deep sequencing and ddPCR.

Conclusion

Our findings expand the clinical and molecular spectrum of RET variants in HSCR and reveal a high frequency of RET DNVs in the Chinese population.

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Title: Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations
Authors: Qian Jiang
Yang Wang
Qi Li
Zhen Zhang
Ping Xiao
Hui Wang
Na Liu
Jian Wu
Feng Zhang
Aravinda Chakravarti
Wei Cai
Long Li
Publication date: 01-12-2019
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2019
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-019-1194-2

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Sequence characterization of RET in 117 Chinese Hirschsprung disease families identifies a large burden of de novo and parental mosaic mutations

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Results

Conclusion

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