Familial Hirschsprung Disease

Gene: GFRA1

Added 'watchlist' tag to be notified of additional cases.

Created: 18 Oct 2017, 9:05 a.m.

Added 'watchlist' tag to be notified of additional cases.

Created: 18 Oct 2017, 9:05 a.m.

Comment on list classification: Updated rating from Red to Amber. Although GFRA1 has a Green expert rating, there is limited literature evidence to support a causation role in Hirschsprung. Further definitive cases are required to form a diagnostic rating.

Created: 18 Oct 2017, 8:40 a.m.

PMID:19282698 determined the prevalence of CAKUT (congenital anomalies of the kidney and urinary tract) in HSCR patients. 84 HSCR patients consecutively admitted to their department between July 2006 and July 2007 underwent analysis. 21 patients with HSCR had associated CAKUT. Variants were found in RET and GDNF but not in GFRA1.

Created: 14 Aug 2017, 12:16 p.m.

Mouse model summarised in PMID:27370713: Total intestinal aganglionosis in homozygotes. Heterozygotes have decreased neuron size but normal numbers. PMID:17507417 also presents mouse model.

Created: 1 Aug 2017, 3:30 p.m.

PMID:9545641 (Angrist et al., 1998) failed to detect linkage of GFRA1 in HSCR patients, and no sequence variants were found to be in significant excess in patients.

Created: 1 Aug 2017, 3:25 p.m.

PMID:12624147 (Borrego et al., 2003) found a large germline deletion in the 5' UTR of GFRA1 of unknown significance in an HSCR case. Analysis of the unaffected father and three unaffected sibs showed this identical deletion.

Created: 1 Aug 2017, 3:22 p.m.

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

animal model confirmation. functional test confirming deleterious variants. digenic

Created: 8 May 2017, 10:36 a.m.

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