Abstract
Woodhouse–Sakati syndrome (WSS) (OMIM#241080) is a rare multi-system autosomal recessive disease with homozygous mutation of the DCAF17 gene. The main features of WSS include diabetes, hypogonadism, alopecia, deafness, intellectual disability and progressive extrapyramidal syndrome. We identified a WSS family with a novel DCAF17 gene mutation type in China. Two unconsanguineous siblings from the Chinese Han family exhibiting signs and symptoms of Woodhouse-Sakati syndrome were presented for evaluation. Whole-exome sequencing revealed a homozygous deletion NM_025000.4:c.1488_1489delAG in the DCAF17 gene, which resulted in a frameshift mutation that led to stop codon formation. We found that the two patients exhibited low insulin and C-peptide release after glucose stimulation by insulin and C-peptide release tests. These findings indicate that the DCAF17 gene mutation may cause pancreatic β cell functional impairment and contribute to the development of diabetes.
Highlights
Woodhouse–Sakati syndrome (WSS), which is a rare autosomal recessive genetic disease, was first reported in 1983 (1)
We have found that b cell function defects may be the main mechanism for the development of diabetes in WSS, which suggests that insulin should probably be the main treatment for patients with WSS when diabetes occurs
Further tests revealed the presence of low insulin secretion, which suggests that b cell functional defects due to DCAF17 gene mutation are among possible mechanisms for the development of diabetes in WSS
Summary
WSS, which is a rare autosomal recessive genetic disease, was first reported in 1983 (1). We identified a WSS family in China and found a novel DCAF17 deletion mutation via genetic testing. Two patients in this family were affected with clinical features of diabetes, alopecia, intellectual disability, hypogonadism, anemia and thrombocytopenia. Phenolyzer suggested that WSS was the most likely disease that can explain the syndrome phenotypes of the proband, and the DCAF17 gene was the candidate gene (Supplementary Figure 1). Sanger sequencing analysis showed the identified c.1488_1489delAG (deletion of nucleotide AG in coding region 1488-1489) was segregated with the disease in this family, which was in homozygous status in the proband’s affected sibling (II-2) and heterozygous status in the proband’s unaffected parents (I-1 and I-2) and sibling (II-3) (Figure 1A). According to the ACMG/AMP criteria, the raw homozygous frameshift variant DCAF17: c.1488_1489delAG was classified as a pathogenic variant for WSS
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
