Gastrointestinal neuromuscular disorders

Gene: RET

Comment on list classification: Clinical overlap with Hirschsprung.

Created: 25 Oct 2016, 4 p.m.

I don't know

See PMID: 23605783 as a review of Hirschsprung disease (HSCR): "most commonly presents sporadically with reduced penetrance and male predominance, although it can be familial and may be inherited as autosomal dominant or autosomal recessive. In 70% of cases, HSCR occurs as an isolated trait and in the other 30% HSCR is associated with other congenital malformation syndromes. HSCR has a complex genetic etiology with several genes and loci being described as associated with either isolated or syndromic forms."..."the RET proto-oncogene is considered the major disease causing gene in HSCR. A common RET variant within the conserved transcriptional enhancer sequence in intron 1 has been shown to be associated with a great proportion of sporadic cases and could act as a modifier by modulating the penetrance of mutations in other genes and possibly of those mutations in the RET proto-oncogene itself. "

Created: 19 Oct 2016, 10:20 a.m.

I am unsure whether this gene should be green due to the contribution of variants in other genes, such as EDNRB, may modulate the disease and a complex, polygenic mechanism of inheritance has been suggested. See publications. PMID: 9090527 - report case of a child with severe Hirschsprung disease (total colonic aganglionosis with small bowel involvement) who had a homozygous variant in the RET gene. Most other variants reported seem to be heterozygous.

Created: 19 Oct 2016, 9:35 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 8114938
• 8114939
• 9090527
• 7581377
• 9700200
• 9760196
• 10090908
• 8001158
• 10090908
• 10922382
• 15829955
• 23605783

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice