LETTER TO JMG

Single nucleotide polymorphic alleles in the 5' region of the RET proto-oncogene define a risk haplotype in Hirschsprung’s disease

M Sancandi¹, P Griseri¹, B Pesce¹, G Patrone¹, F Puppo¹, M Lerone¹, G Martucciello², G Romeo⁴, R Ravazzolo³, M Devoto⁵, I Ceccherini¹

¹ Laboratorio di Genetica Molecolare, Istituto G Gaslini, Genova, Italy
² Divisione e Cattedra di Chirurgia Pediatrica, Istituto G Gaslini, Genova, Italy
³ Laboratories di Genetica Moleculare, Istituto G Gaslini, Genova, Italy
⁴ Cattedra di Genetica Medica, Università di Bologna, Bologna, Italy
⁵ Department of Research, Nemours Children’s Clinic, Wilmington, Delaware, USA

Correspondence to:
Correspondence to:
Isabella Ceccherini, Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, L.go G Gaslini 5, 16148 Genova, Italy;
isa.c@unige.it

Keywords: Hirschsprung’s disease; RET proto-oncogene; single nucleotide polymorphism; gene promoter

The first 150 words of the full text of this article appear below.

Hirschsprung’s disease is a congenital disorder characterised by intestinal obstruction caused by the absence of parasympathetic intrinsic ganglion cells along variable lengths of the colon.¹ The high proportion of sporadic cases (80–90%), the variable expressivity, the incomplete sex dependent penetrance, and the involvement of several genes, most of which are yet to be identified, show a complex pattern of inheritance for this disorder.^2–4 The RET proto-oncogene is the major gene involved in Hirschsprung’s disease, accounting for a high proportion of both familial (about 50%) and sporadic cases (10–15%). Five to ten per cent of patients show alterations in other genes such as the glial cell line derived neurotrophic factor (GDNF), neurturin (NTN), endothelin 3 (EDN3), endothelin B receptor (EDNRB), endothelin converting enzyme 1 (ECE1), transcriptional factor SOX10, and Smad interacting protein 1 (SIP1).^1,5 The small number of . . . [Full text of this article]

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