The DCAF17 gene, also known as C2ORF37, comprises 520 amino acids and weights about 59 kDa. It encodes a nuclear transmembrane protein, which may functions as a substrate receptor for the CUL4-DDB1 E3 ubiquitin-protein ligase complex. Defects in this protein are the cause of Woodhouse-Sakati syndrome, a rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome.
The DCAF17 gene was mapped to 2q31.1 chromosome. It consists of 14 coding exons and spans approximately 51 kb. Nonsense, splice site and frameshift mutations have been identified in the DCAF17 gene associated with Woodhouse-Sakati syndrome.
Ben-Omran et al. (2011) reported seven patients (four males and three females) from two related Qatari families with Woodhouse-Sakati syndrome. Mutation in the C2ORF37 gene was identified in the affected patients.
Alazami et al. (2008) performed genome-wide linkage analysis on Saudi patients affected with Woodhouse Sakati syndrome, and identified an extended autozygous region on chromosome 2q with this condition. This region was further narrowed to a 1.2 Mb region by the inclusion of an additional family with four affected siblings. Sequencing of a hypothetical gene, C2ORF37, in this region revealed a 1bp deletion mutation (c.436delC) in exon 4 that fully segregated with the phenotype. The deletion is predicted to cause a frameshift in the beta-isoform of the protein and results in premature termination.. This mutation was found in six additional affected Saudi families, but not in 274 Saudi control chromosomes. SNP-based haplotype analysis confirmed a founder effect, and the deletion likely arose approximately 55 generations earlier.
Hdiji et al., (2016) described two sisters with Woodhouse-Sakati syndrome born to healthy first cousin parents. The index patient was a 25-year-old woman who presented with generalized dystonia involving the trunk and all four limbs. She had dysmorphic facial features including a triangular shape with a large forehead, sparse eyebrows and eyelashes, alopecia predominant in the fronto-temporal region of the scalp, hypertelorism, large ears, prominent nasal root, precocious skin aging and partial edentulism. She also had mild intellectual disabilities. Her secondary sexual characteristics were absent with minimal breast budding and marked vulvar hypoplasia, as well as no facial, axillary or pubic hair. She was severely disabled and wheelchair dependent because of her movement disorder. Her laboratory tests revealed hypogonadotropic hypogonadism. Her 30-year-old sister presented at the age of 12 years with dystonic movement of the left upper limb. Eight years later, her right side became affected. At the age of 27 years she had walking difficulties with frequent falls, and one year later she became bedridden. She had intellectual disabilities. She had a primary amenorrhea and alopecia. She had the same dysmorphic facial characteristics as her sister. Sequencing of the C2orf37 gene revealed a homozygous mutation c.436delC in exon 4 in the two affected sisters, and in a heterozygous state in the parents and the healthy sister.
To contribute with your findings to the content of this record, please fill the CTGA Database Information Submission Form and email it, along with supportive documents, to firstname.lastname@example.org.