J Pediatr Genet 2022; 11(03): 240-244
DOI: 10.1055/s-0040-1718385
Case Report

Novel Causative RET Mutation in a Japanese Family with Hirschsprung's Disease: Case Report and Factors Impacting Disease Severity

1   Department of General Pediatrics, Nagano Children's Hospital, Azumino, Japan
2   Life Science Research Center, Nagano Children's Hospital, Azumino, Japan
,
Kazuki Yoshizawa
3   Department of Pediatric Surgery, Nagano Children's Hospital, Azumino, Japan
,
Tomoko Hatata
3   Department of Pediatric Surgery, Nagano Children's Hospital, Azumino, Japan
,
Katsumi Yoshizawa
3   Department of Pediatric Surgery, Nagano Children's Hospital, Azumino, Japan
,
Shigeru Takamizawa
3   Department of Pediatric Surgery, Nagano Children's Hospital, Azumino, Japan
,
Jun Kobayashi
2   Life Science Research Center, Nagano Children's Hospital, Azumino, Japan
4   Department of Clinical Laboratory, Nagano Children's Hospital, Azumino, Japan
,
Noriko Kubota
2   Life Science Research Center, Nagano Children's Hospital, Azumino, Japan
4   Department of Clinical Laboratory, Nagano Children's Hospital, Azumino, Japan
,
Eiko Hidaka
2   Life Science Research Center, Nagano Children's Hospital, Azumino, Japan
4   Department of Clinical Laboratory, Nagano Children's Hospital, Azumino, Japan
› Institutsangaben

Funding This study was financially supported by JSPS KAKENHI, under grant nos.: JP16H00645, JP17H00639, and JP19H00445.
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Abstract

RET gene variances confer susceptibility to Hirschsprung's disease (HSCR) with pathogenetic mutations being identified in half of familial cases. This investigation of familial HSCR was aimed to clarify the relationship between genetic mutations and clinical phenotype using next-generation sequencing. A novel c2313C > G(D771E) RET mutation was identified in all three affected family members. The mutation involved the kinase domain, which is believe to impair RET activity and intestinal function. A second RET mutation, c1465G > A(D489N), was found only in the extensive aganglionosis case. We conclude that the novel c2313C > A(D771E) mutation in RET may be pathogenic for HSCR, while the c1465C > G(D489N) mutation may be related to phenotype severity.

Ethical Approval

The study was conducted following approval from the Nagano Children's Hospital Ethics Committee (Approval number: 27–34) and in accordance with the guidelines outlined in the Declaration of Helsinki.




Publikationsverlauf

Eingereicht: 20. Juli 2020

Angenommen: 29. August 2020

Artikel online veröffentlicht:
05. Oktober 2020

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