Hypogonadotropic hypogonadismGene: 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.
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.
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
Gene: dcaf17 has been classified as Green List (High Evidence).
28th Oct 2016: This panel was revised after external expert review and internal discussion. For several genes that have been shown to contribute to the disorder in a digenic/polygenic manner, the decision was made to only include genes as green if biallelic variants had been reported independently from other genes. Genes with a monoallelic mechanism, that have been shown in some studies in conjunction with variants in other genes, were made red as monoallelic variants in these genes may not provide a complete diagnosis.
This gene has been classified as Red List (Low Evidence).
Phenotypes for DCAF17 were set to Woodhouse-Sakati syndrome 241080
DCAF17 was created by ellenmcdonagh
DCAF17 was added to Idiopathic hypogonadotropic hypogonadismpanel. Sources: Literature