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

Tsukasa Higuchi; Kazuki Yoshizawa; Tomoko Hatata; Katsumi Yoshizawa; Shigeru Takamizawa; Jun Kobayashi; Noriko Kubota; Eiko Hidaka

doi:10.1055/s-0040-1718385

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

J Pediatr Genet. 2020 Oct 5;11(3):240-244. doi: 10.1055/s-0040-1718385. eCollection 2022 Sep.

Authors

Tsukasa Higuchi^{1

2}, Kazuki Yoshizawa³, Tomoko Hatata³, Katsumi Yoshizawa³, Shigeru Takamizawa³, Jun Kobayashi^{2

4}, Noriko Kubota^{2

4}, Eiko Hidaka^{2

4}

Affiliations

¹ Department of General Pediatrics, Nagano Children's Hospital, Azumino, Japan.
² Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.
³ Department of Pediatric Surgery, Nagano Children's Hospital, Azumino, Japan.
⁴ Department of Clinical Laboratory, Nagano Children's Hospital, Azumino, Japan.

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.

Keywords: Hirschsprung's disease; RET; next-generation sequencing.

Publication types

Case Reports

Grants and funding

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