Is Hirschsprung disease a mendelian or a multifactorial disorder?
['Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes', "In this study, we review the identification of genes and loci involved in the non-syndromic common form and syndromic Mendelian forms of Hirschsprung's disease. The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease. The non-Mendelian inheritance of sporadic non-syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model", 'Coding sequence mutations in e.g. RET, GDNF, EDNRB, EDN3, and SOX10 lead to long-segment (L-HSCR) as well as syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). Furthermore, mutations in the RET gene are responsible for approximately half of the familial and some sporadic cases, strongly suggesting, on the one hand, the importance of non-coding variations and, on the other hand, that additional genes involved in the development of the enteric nervous system still await their discovery', 'For almost all of the identified HSCR genes incomplete penetrance of the HSCR phenotype has been reported, probably due to modifier loci. Therefore, HSCR has become a model for a complex oligo-/polygenic disorder in which the relationship between different genes creating a non-mendelian inheritance pattern still remains to be elucidated', ' Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes.', ' The inheritance of Hirschsprung disease is generally consistent with sex-modified multifactorial inheritance with a lower threshold of expression in males.', 'Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes.', 'Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability.', 'BACKGROUND: RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology.', 'In the etiology of Hirschsprung disease various genes play a role; these are: RET, EDNRB, GDNF, EDN3 and SOX10, NTN3, ECE1, Mutations in these genes may result in dominant, recessive or multifactorial patterns of inheritance.', "Chromosomal and related Mendelian syndromes associated with Hirschsprung's disease.", "The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease", 'In the etiology of Hirschsprung disease various genes play a role; these are: RET, EDNRB, GDNF, EDN3 and SOX10, NTN3, ECE1, Mutations in these genes may result in dominant, recessive or multifactorial patterns of inheritance', 'On the basis of a skewed sex-ratio (M/F = 4/1) and a risk to relatives much higher than the incidence in the general population, HSCR has long been regarded as a sex-modified multifactorial disorder', 'The inheritance of Hirschsprung disease is generally consistent with sex-modified multifactorial inheritance with a lower threshold of expression in males', "The non-Mendelian inheritance of sporadic non-syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model"]
["Coding sequence mutations in RET, GDNF, EDNRB, EDN3, and SOX10 are involved in the development of Hirschsprung disease. The majority of these genes was shown to be related to Mendelian syndromic forms of Hirschsprung's disease, whereas the non-Mendelian inheritance of sporadic non-syndromic Hirschsprung disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model."]
[]