Familial Hirschsprung Disease

Gene: NRTN

Comment when marking as ready: Marked as ready: 14th August 2017.

Created: 14 Aug 2017, 2:41 p.m.

Comment on list classification: Kept rating as Red: Although NRTN is on the original submitted list, publications report co-occurence of Neurturin and RET variants in HSCR patients. Plus red expert review.

Created: 14 Aug 2017, 2:41 p.m.

PMID:21206993 (Ruiz-Ferrer et al., 2011) report association of NRTN gene with HSCR. Mutational screening of GDNF, NRTN, ARTN and PSPN was performed on 217 patients with HSCR (199 sporadic cases and 27 familial cases belonging to 13 different families). The authors identify a F127L variant in NRTN in a sporadic Hirschsprung patient: functional analysis shows that F127L results in reduced phosphorylation of RET. All patients were found to be homozygous or heterozygous for the common RET variant within the transcriptional enhancer in intron 1 of RET.

Created: 3 Aug 2017, 2:33 p.m.

Added polygenic tag based on co-occurring RET and NRTN mutations in patients in PMID:9700200.

Created: 3 Aug 2017, 10:55 a.m.

Neurturin is a ligand for the receptor RET. PMID:9700200 (Doray et al 1998) report a heterozygous missense NRTN mutation in a large non-consanguineous family including 4 children affected with a severe aganglionosis phenotype extending up to the small intestine. It appears that the NRTN mutation reported here is not sufficient to cause HSCR, and this multiplex family also segregates a RET mutation.

Created: 3 Aug 2017, 10:40 a.m.

Publications

• 9700200

Red List (low evidence)