Case Report: A Chinese Family of Woodhouse-Sakati Syndrome With Diabetes Mellitus, With a Novel Biallelic Deletion Mutation of the DCAF17 Gene

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.

Keywords: Woodhouse–Sakati syndrome; alopecia; diabetes; hypogonadism; intellectual disability.

Figure 1

Pedigree and Sanger sequencing chromatograms of the identified disease-causing variants. (A) Pedigree of the WSS family. Marks ‘+/+’ and ‘+/-’ indicate the homozygous status and heterozygous status of the identified the DCAF17:c.1488_1489delAG respectively. (B) Sanger sequencing chromatograms of the DCAF17:c.1488_1489delAG in homozygous status (above) and heterozygous status (below).

Figure 2

Photographs of the WSS patients. (A, B) The proband’s hair, eyebrows and eyelashes are sparse, and infantile external genitalia. (C, D) The brother of proband: childhood-onset hair thinning, His hair, eyebrows and eyelashes are further sparse in adulthood.

Figure 3

The images of the WSS patients. (A) Computed tomography of the abdomen of the proband demonstrated atrophy of the pancreas. (B) Computed tomography of the abdomen of the brother of proband showed uneven pancreatic density. (C, D) Pituitary MR of the brother of proband indicated the empty sella and none pituitary gland. (E) Hip CT of the brother of proband suggested osteoporosis that was not consistent with actual age. (arrows).