Non-syndromic familial congenital anorectal malformations

Gene: GLI3

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pallister-Hall syndrome

Comment on list classification: Rating as green as sufficient evidence of association with Pallister-Hall
syndrome, which has anorectal malformation as part of the phenotype and potential early presentation of anorectal anomalies. This has been checked with the Genomics England clinical team

Created: 2 Oct 2018, 3:57 p.m.

This gene is associated with Pallister-Hall syndrome in OMIM. Anorectal malformations is one of the phenotypes observed in this syndrome. 2 families have been reported with Pallister-Hall syndrome (PMID: 9054938; 10945658] and a variant in GLI3. Both families report some individuals with anorectal malformations. Stoll et al. (2001) (PMID: 11693785) described a patient considered to have Pallister-Hall syndrome in whom they could not identify a mutation in the GLI3 gene. A mutation was found in the GLI1 gene. Other cases of GLI3 variants in Pallister-Hall syndrome patients have been found but not always with reports of the anorectal malformation phenotype e.g. PMID: 21108399; 29204208.

Created: 26 Sep 2018, 12:29 p.m.

Comment on list classification: Rated as Amber as is on expert list.

Created: 19 Sep 2018, 4:17 p.m.

Gene added from expert list from Dr Charles Shaw-Smith (Royal Devon and Exeter NHS Foundation Trust)

Created: 19 Sep 2018, 4:17 p.m.