The DCAF17 gene is located on chromosome 2 at 2q31.1 and encodes the DDB1 and CUL4 associated factor 17 protein, which is involved in protein ubiquitination. DCAF17 was first reported in relation to autosomal recessive Woodhouse-Sakati Syndrome in 2008 (Alazami et al., 2008 PMID 19026396). At least 18 nonsense, frameshift or splice site variants in DCAF17 have been reported in humans (Alazami et al., 2008, PMID 19026396; Alazami et al., 2010 PMID 20507343; Habib et al., 2011 PMID 21963443; Abdulla et al., 2015 PMID 26440089; Ali et al., 2016 PMID 26612766; Gurbuz et al., 2017 PMID 29178422; Sendur et al., 2019 PMID 31152917; Kurmaz et al., 2019 PMID 31472064; Louro et al., 2019 PMID 31347785; Shah et al., 2020 PMID 31323129). Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least 22 probands in 15 publications. Variants in this gene segregated with disease in additional family members. The mechanism for disease is biallelic loss of function variants. This gene-disease association is supported by expression studies and mouse models that reproduce part of the human phenotype Alazami et al., 2008, PMID 19026396; Gurbuz et al., 2017, PMID 29178422; Ali et al., 2018, PMID 29907856). Male DCAF17 knockout mice have hypogonadism and infertility.
In summary, biallelic loss of function variants in DCAF17 are definitely associated with autosomal recessive Woodhouse-Sakati Syndrome. Woodhouse Sakati syndrome is a recognizable condition that is often clinically diagnosed. The association between DCAF17 and Woodhouse-Sakati syndrome has been repeatedly demonstrated in clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Syndromic Disorders Gene Curation Expert Panel on the meeting date 18Dec2020 (SOP Version 7).
DCAF17 was first reported in relation to autosomal recessive Woodhouse-Sakati Syndrome in 2008 (Alazami et al 2008, PMID 19026396). At least 18 nonsense, frameshift or splice site variants have been reported in humans (Alazami et al 2008, PMID 19026396; Alazami et al 2010 PMID 20507343; Habib et al 2011, PMID 21963443; Abdulla et al 2015, PMID 26440089; Ali et al 2016, PMID 26612766; Gurbuz et al 2017, PMID 29178422; Sendur et al 2019, PMID 31152917; Kurmaz et al 2019, PMID 31472064; Louro et al 2019, PMID 31347785; Shah et al 2020, PMID 31323129). Evidence supporting this gene-disease relationship includes case-level data and experimental data.
Summary of case level data: 10.5 points. Variants in this gene have been reported in at least 22 probands in 15 publications. Variants in this gene segregated with disease in additional family members. The mechanism for disease is homozygous loss of function.
Experimental evidence: 1.5 points This gene-disease association is supported by expression studies and mouse models that reproduce part of the human phenotype Alazami et al 2008, PMID 19026396; Gurbuz et al 2017, PMID 29178422; Ali et al 2018, PMID 29907856).
In summary, DCAF17 is definitely associated with autosomal recessive Woodhouse-Sakati Syndrome. This has been repeatedly demonstrated in clinical diagnostic settings, and has been upheld over time.
This classification was approved by the ClinGen Syndromic disorders Working Group on December 18. 2020 (SOP v8).
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