Woodhouse-Sakati Syndrome via the DCAF17 Gene

Woodhouse-Sakati syndrome is a rare multi-systemic disorder. This syndrome belongs to a heterogeneous group of neurodegeneration with brain iron accumulation. Woodhouse-Sakati syndrome manifests during adolescence and includes alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Only in certain patients, brain MRI shows iron deposition the globus pallidus and substantia nigra. Decreased signal was also observed in the globus pallidus, substantia nigra, and other regions of the basal ganglia (Alazami et al. 2008; Alazami et al. 2010; Hdiji et al. 2016; Arber et al. 2016).

Pathogenic variants in the DCAF17 gene are causative for Woodhouse-Sakati syndrome which is inherited in an autosomal recessive manner. The DCAF17 gene encodes DDB1-and-CUL4-associated factor 17 that is expressed in the nucleolus with unknown function. Pathogenic variants in the DCAF17 gene include nonsense, frameshift, and splice mutations. Pathogenic DCAF17 missense variants have not been described, and current information suggests Woodhouse-Sakati syndrome results from loss of DCAF17 function (Alazami et al. 2008; Human Gene Mutation Database).

Woodhouse-Sakati syndrome is a very rare disease, however, clinical sensitivity may be high in patients meeting clinical and histological criteria for this disorder.

This test provides full coverage of all coding exons of the DCAF17 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).