Woodhouse-Sakati Syndrome: Report of the First Tunisian Family with the <i>C2orf37</i> Gene Mutation

Abstract

Woodhouse-Sakati syndrome (WSS) is an infrequent autosomal recessive condition characterized by progressive extrapyramidal signs, mental retardation, hypogonadism, alopecia, and diabetes mellitus. This syndrome belongs to a heterogeneous group of inherited neurodegenerative disorders characterized iron accumulation in the brain, and it is caused by mutations of the C2orf37 gene. We report the first Tunisian family with two affected sisters presenting with a phenotype suggestive of WSS. We examined the index patient presenting with movement disorders and mental retardation and then searched for similar cases in her family, which identified a sister with similar signs. We performed a genetic study that confirmed the diagnosis and revealed a c.436delC mutation of the C2orf37 gene. Therefore, WSS is an important consideration in patients presenting with movement disorders and intellectual disability. A high consanguinity contributes to the clustering of such rare autosomal recessive syndromes.

Woodhouse–Sakati syndrome in a family is associated with a homozygous start loss mutation in the DCAF 17 gene

“…To date, the disease has been reported in a number of different populations including those from the Middle East, Northern and Eastern Europe, Turkey and South Asia. 3 Homozygous and compound heterozygous sequence variants in the DDB1-and CUL4-associated factor 17 gene (DCAF17; MIM 612515) are associated with WSS. 1,2,4,5 The exact pathogenesis mechanism is still unknown, but it is hypothesized that the disease may result from defective nucleolar function affecting cell cycle regulation or cellular ageing.…”

Woodhouse-Sakati Syndrome With Psychosis and Basal Ganglia Calcification: A Case Report

“…Because defects in DCAF17 (OMM312515) are responsible for causing the disease, the patient was tested for mutations of this gene, and her genetic testing revealed homozygous disease-causing single nucleotide deletion (C.436delC) of frameshift mutation (p.A147HfsX9) in exon 4 of the gene DCAF17 gene. This mutation has been previously reported in patients with Woodhouse Sakati syndromes [9][10][11]. In spite of being rare, Woodhouse syndrome should be considered in patients presenting with combinations of neuropsychological, endocrinal, and ectodermal manifestations, especially in the Middle East and Arab world.…”

“…The calcification seems to be idiopathic because her calcium profile was normal. Previous reported studies reported variable brain imaging abnormalities; some patients had variable abnormalities at deep white matter [6,7], whereas others had iron deposition in globus pallidus [8,9].…”

“…In spite of being rare, Woodhouse syndrome should be considered in patients presenting with combinations of neuropsychological, endocrinal, and ectodermal manifestations, especially in the Middle East and Arab world. To date, only few dozens of families were reported to have the disease, especially in Saudi Arabia [5,6,11], Pakistan [12], Tunisia [9], Turkey [13], Croatia [14], India [15], and Italy [16]. The cases reported have various clinical, phenotypic, and genotypic patterns.…”

In silicoanalysis of coding SNPs and 3′-UTR associated miRNAs inDCAF17gene that may affect the regulation and pathogenesis of Woodhouse-Sakati Syndrome

“…Woodhouse-Sakati Syndrome (WSS, MIM: 241080) is a rare autosomal-recessive multi systemic disorder which is characterized by a combination of hypogonadism, alopecia, Diabetes Mellitus (DM), mental retardation and extrapyramidal signs. (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) It was originally described in a number of consanguineous Saudi families in the Middle East, but has recently been reported in other ethnicities as well. (11,12) Since its original description in 1983, approximately 50 cases have been reported until now.…”