Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease.

  title={Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease.},
  author={Tania Atti{\'e} and Anna Pelet and Patrick Edery and Charis Eng and Lois M. Mulligan and Jeanne Amiel and L. Boutrand and Ch{\'e}rif Beldjord and Claire Nihoul-F{\'e}k{\'e}t{\'e} and Arnold Munnich},
  journal={Human molecular genetics},
  volume={4 8},
Hirschsprung disease (HSCR) is a common congenital malformation (1 in 5,000 live births) due to the absence of autonomic ganglia in the terminal hindgut, and resulting in intestinal obstruction in neonates. Recently, a dominant gene for familial HSCR has been mapped to chromosome sub-band 10q11.2 and the disease has been ascribed to mutations in a tyrosine kinase receptor gene mapping to this region, the RET proto-oncogene. Studying the 20 exons of the RET gene by a combination of denaturating… 

Frequency of RET mutations in long‐ and short‐segment Hirschsprung disease

The approach of single‐strand conformational polymorphism analysis established for all the 20 exons of the RET proto‐oncogene, and previously used to screen for point mutations in Hirschsprung patients, allowed us to identify seven additional mutations among 39 sporadic and familial cases of HirschSprung disease.

Recurrence of Hirschsprung disease due to maternal mosaicism of a novel RET gene mutation

A family with recurrence of L-HSCR in two siblings due to a novel RET mosaic mutation in the unaffected mother is reported, wondering whether this is a truly unique family or whether the true frequency of somatic and germ-line mosaicism is underestimated in HSCR.

A rare haplotype of the RET proto-oncogene is a risk-modifying allele in hirschsprung disease.

The role of a single-nucleotide polymorphism, 2508C-->T (S836S), in exon 14 of the RET gene, characterized by low frequency among patients with HSCR and overrepresentation in individuals affected by sporadic medullary thyroid carcinoma is investigated.

Molecular-genetic analysis of Hirschsprung's disease in South Africa

It is demonstrated that all the potential disease-related mutations identified in South African patients with sporadic HSCR occur in the RET gene.

Novel RET mutations in Hirschsprung's disease patients from the diverse South African population

This study represents the first comprehensive genetic analysis of HSCR in the diverse South African population and identifies five novel mutations and one previously described mutation.

RET genotypes comprising specific haplotypes of polymorphic variants predispose to isolated Hirschsprung disease

The data suggest that genotypes comprising specific pairs of REThaplotypes are associated with predisposition to HSCR either in a simple autosomal recessive manner or in an additive, dose dependent fashion.

Segregation at three loci explains familial and population risk in Hirschsprung disease

Oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a parent-of-origin effect at RET are shown.

Haplotypes of the Human RET Proto‐oncogene Associated with Hirschsprung Disease in the Italian Population Derive from a Single Ancestral Combination of Alleles

The results suggests the possibility that a common HSCR predisposing variant is located further downstream than the previously suggested interval encompassing intron 1, and two disease‐associated haplotypes derive from a single founding locus, extending up to intron 19 and successively rearranged in correspondence with a high recombination rate region located between the proximal and distal portions of the gene.