Differences in sex development

Gene: WT1

Green List (high evidence)

As discussed in the GMS Endocrinology Specialist Test Group webex call 28th Jan 2019: The Specialist Test Group agreed that there is enough evidence to rate this gene green.

Created: 29 Apr 2019, 9:46 a.m.

Comment on mode of inheritance: Changed from 'other' to reflect review.

Created: 3 Apr 2017, 5:08 p.m.

Comment when marking as ready: Associated with phenotypes in OMIM and G2P / DD. At least 11 variants reported in Denys-Drash syndrome 194080, 5 in Frasier syndrome 136680 and one in Meacham syndrome 608978

Created: 12 Sep 2016, 2:59 p.m.

Comment on mode of inheritance: Monoallelic inheritance and somatic mutation recorded as MOI for Denys-Drash syndrome 194080; Frasier syndrome 136680. MOI unknown for Meacham syndrome 608978

Created: 12 Sep 2016, 2:55 p.m.

Comment on phenotypes: Variants also reported in Mesothelioma, somatic 156240, Nephrotic syndrome, type 4 256370 and Wilms tumor, type 1 194070

Created: 12 Sep 2016, 2:52 p.m.

Green List (high evidence)

Deletion of WT1 and mild genital changes (usually) can be part of WAGR syndrome. Typically exon 9 splice mutations cause Frasier syndrome, with testicular dysgenesis, gonadoblastoma risk, severe underandrogenization, and milder renal abnormalities such a FSGS. Other changes (often point mutations in zinc fingers) cause Denys-Drash syndrome, with severe hypospadias, MCGS, and Wilms Tumor risk. Meacham syndrome with diaphragmatic hernia also reported. There can be phenotypic and genotypic overlap. Careful consideration needed for reporting back as counselling needed for tumor risk and associated features.

Created: 4 Feb 2016, 4:23 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Testicular dysgenesis with renal abnormalities