Gastrointestinal neuromuscular disorders

Gene: RET

Green List (high evidence)

RET (ret proto-oncogene)
EnsemblGeneIds (GRCh38): ENSG00000165731
EnsemblGeneIds (GRCh37): ENSG00000165731
OMIM: 164761, Gene2Phenotype
RET is in 21 panels

3 reviews

Richard Scott (Genomics England Curator)

Comment on list classification: Clinical overlap with Hirschsprung.
25 Oct 2016, 4 p.m.

Ellen McDonagh (Genomics England Curator)

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

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

Neil shah (GOSH)

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

History Filter Activity

26 Oct 2016, Gel status: 4

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

26th October 2016: panel revised after expert review and further curation of the analysis, with then internal clinical review. Ready for promotion to version 1.

25 Oct 2016, Gel status: 4

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for RET were set to 8114938; 8114939; 9090527; 7581377; 9700200; 9760196; 10090908; 8001158; 10090908; 10922382; 15829955;11953745

19 Oct 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for RET were set to 8114938; 8114939; 9090527; 7581377; 9700200; 9760196; 10090908; 8001158; 10090908; 10922382; 15829955

19 Oct 2016, Gel status: 2

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for RET was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Oct 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

31 Aug 2016, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for RET were set to {Hirschsprung disease, susceptibility to, 1} 142623

31 Aug 2016, Gel status: 3

Added New Source

Sarah Leigh (Genomics England Curator)

RET was added to Neonatal and familial gastrointestinal neuromuscular disorderspanel. Source: UKGTN

31 Aug 2016, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

RET was added to Neonatal and familial gastrointestinal neuromuscular disorderspanel. Source: Radboud University Medical Center, Nijmegen

31 Aug 2016, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

RET was created by sleigh

31 Aug 2016, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

RET was added to Neonatal and familial gastrointestinal neuromuscular disorderspanel. Sources: Illumina TruGenome Clinical Sequencing Services