Screening of the RET gene of Vietnamese Hirschsprung patients identifies 2 novel missense mutations.
OBJECTIVE
Hirschsprung disease (HSCR; megacolon, congenital aganglionosis) is a congenital disorder characterized by the absence of ganglion cells along variable segments of the gut. Both rare (RV) and common variants of the RET gene are associated with HSCR. The aim of this study is to assess, for the first time, the variation in the RET gene of Vietnamese HSCR patients.


METHODS
We used Sanger sequencing to screen the coding sequence of the RET gene of 97 Vietnamese HSCR patients of Southern Chinese ancestry. The healthy population consisted of 250 Southern Chinese individuals with no diagnosis of HSCR.


RESULTS
We detected 8 heterozygous RVs distributed among 13 patients (13.40%) and that were not present in healthy individuals. Among those variants, there were 2 novel and deleterious (R133C [c.397 C>T]; R144C [c.430 C>T]) missense amino acid substitutions, 2 novel silent variants (P667P [c.2001 A>T]; Y809Y [c.2427 C>T]), and 4 previously described missense substitutions (R114H [c.341 G>A]; V292M [c.874 G>A]; G533S [c.1597 G>A]; R982C [c.2944 C>T]). As expected, the common RET coding sequence variants rs1800858 (A45A [c.135 G>A]) and rs1800861 (L769L [c.2307 T>G]) were highly associated with the disease.


CONCLUSIONS
The identification of novel deleterious variants together with the fact RET RVs are virtually unique to HSCR patients indicates that the RET gene is a target for mutations among Hirschsprung patients of any population.
Department of Human Genetics, National Hospital of Pediatrics, Hanoi, Vietnam.
Diem-Ngoc
DN
Ngo
Man-Ting
MT
So
Hongsheng
H
Gui
Anh-Quynh
AQ
Tran
Duc-Hau
DH
Bui
Stacey
S
Cherny
Paul Kwong-Hang
PK
Tam
Thanh-Liem
TL
Nguyen
Maria-Mercè
MM
Garcia-Barcelo
D044466:Asian People / Q000235:genetics; D002648:Child; D005260:Female; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*
D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human