A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10

  title={A gene for Hirschsprung disease maps to the proximal long arm of chromosome 10},
  author={Stanislas Lyonnet and Alessandra Bolino and Anna Pelet and Laurent Abel and Claire Nihoul-F{\'e}k{\'e}t{\'e} and M. L. Briard and V. Mok-Siu and Helena K{\aa}{\aa}ri{\aa}inen and Giuseppe Martucciello and Margherita Lerone and Aldamaria Puliti and Yin Luo and Jean Weissenbach and Marcella Devoto and Arnold Munnich and Giovanni Romeo},
  journal={Nature Genetics},
Hirschsprung disease (HSCR) is a frequent congenital disorder (1 in 5,000 newborns) of unknown origin characterized by the absence of parasympathetic intrinsic ganglion cells of the hindgut. Taking advantage of a proximal deletion of chromosome 10q (del 10q11.2–q21.2) in a patient with total colonic aganglionosis, and of a high–density genetic map of microsatellite DNA markers, we performed genetic linkage analysis in 15 non–syndromic long–segment and short–segment HSCR families. Multipoint… 
Mutations of the RET proto-oncogene in Hirschsprung's disease
No recombination was observed between the disease locus and the locus for the RET proto-oncogene, a protein tyrosine kinase gene expressed in the cells derived from the neural crest, and it is shown that the mutant genotypes segregate with the disease in HSCR families.
Genetics of Hirschsprung disease
HSCR has become a model of a complex polygenic disorder in which the interplay of different genes is currently being elucidated, and for almost every HSCR gene, incomplete penetrance of the H SCR phenotype has been observed.
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.
Hirschsprung disease, associated syndromes and genetics: a review
Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment, which stands as a model for genetic disorders with complex patterns of inheritance.
Hirschsprung's disease associated with a deletion of chromosome 10 (q11.2q21.2): a further link with the neurocristopathies?
A patient with total colonic aganglionosis in association with a deletion of part of the long arm of chromosome 10 includes the ret proto-oncogene, which has recently been implicated in multiple endocrine neoplasia type 2A (MEN 2A).
Familial form of hirschsprung disease: nucleotide sequence studies reveal point mutations in the RET proto-oncogene in two of six families but not in other candidate genes.
The DNA sequences of 5 further genes (GDNF, GDNFRalpha, EDN3, EDNRB, and NTN), that may contribute to the development of HSCR, have not shown mutations in the patients analyzed so far.
Long segment and short segment familial Hirschsprung's disease: variable clinical expression at the RET locus.
The data suggest that the two anatomical forms of familial HSCR, which have been separated on the basis of clinical and genetic criteria, may be regarded as the variable clinical expression of mutations at the RET locus.
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.
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.
Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung's disease
The hypothesis that RET, in addition to its potential role in tumorigenesis, plays a critical role in the embryogenesis of the mammalian enteric nervous system is supported.


Deleted and normal chromosome 10 homologs from a patient with Hirschsprung disease isolated in two cell hybrids through enrichment by immunomagnetic selection.
A cytogenetically undetectable deletion was observed in a patient with total colonic aganglionosis with small bowel involvement (TCSA), a variant of Hirschsprung disease, and it is hypothesized that they originate from mutations in different genes clustered in the centromeric region of 10q.
A genetic study of Hirschsprung disease.
A model of gene action with random effects during morphogenesis is compatible with observations, and an increased sex ratio and an elevated risk to sibs are observed.
Familial aspects of Hirschsprung's disease.
Neuronal intestinal dysplasia in a parent was associated with total colonic aganglionosis in two siblings of one family which suggests a similar genetic inheritance pattern to HD.
Hirschsprung disease: a genetic study
This study examines the association of Hirschsprung disease with Down syndrome and calculates the recurrence risk for families of Hirshsprung patients and examines the relationship between histologically diagnosed patients and Down syndrome.
Association of megacolon with a new dominant spotting gene (Dom) in the mouse.
A new semidominant mutation in the mouse is described that produces white spotting and a deficiency of myenteric ganglion cells in the colon and, in homozygotes, is lethal prior to 13 days of gestation.
Interstitial deletion of distal 13q associated with Hirschsprung's disease.
Three cases of interstitial deletion of chromosome 13 involving the common segment 13q22.1----q32.1 are reported. In addition to the recognised clinical features of this deletion, two had
An epidemiological study of Hirschsprung's disease.
  • E. Goldberg
  • Medicine
    International journal of epidemiology
  • 1984
There was a larger percentage of children who were the first births of mothers aged 30 and above, a result previously reported for children with neural tube defects, and among environmental factors studied, there was no time trend and no relationship with socioeconomic status found.