Hypogonadotropic hypogonadism

Gene: DCAF17

Comment on list classification: Promoted from red to green as recommended by Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust) and the evidence presented in her review.

Created: 17 Jan 2019, 1:43 p.m.

Green List (high evidence)

Alazami et al 2008 (PMID 19026396) - identified founder variant (1bp deletion) in eight families of Saudi origin. Three other loss-of-function variants were identified in patients of different ethnicity. Alazami et al 2010 (PMID 20507343) - loss-of-function variants identified in 7 patients with Woodhouse-Sakati syndrome from 4 unrelated families of different ethnicity. Gurbuz et al 2018 (PMID: 29178422) - Exome sequencing in 5 women with syndromic hypergonadotrophic hypogonadism from 2 unrelated families. Homozygous variant affecting splice acceptor site identified in 4 Turkish siblings,1 American was compound heterozygous for a stop gain variant in exon 5 (c.C535T; p.Gln179*) and previously described stop gain variant in exon 9 (c.G906A; p.Trp302*). A mouse model mimicking loss of function in exon 2 of Dcaf17 was generated using CRISPR/Cas9 and showed female subfertility and male infertility.

Created: 16 Jan 2019, 11:53 a.m.

Publications

• 19026396
• 20507343
• 29178422

Comment when marking as ready: Associated with the phenotype in OMIM, but not in G2P. One variant reported in a case of Woodhouse-Sakati syndrome with hypogonadotrophic hypogonadism, other reports of hypergonadotrophic hypogonadism associated with variants in DCAF17

Created: 14 Oct 2016, 10:30 a.m.

Came across the association with this phenotype whilst reviewing this gene for the dystonia panel.

Created: 23 Aug 2016, 1:43 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Woodhouse-Sakati syndrome

Publications

• 20507343