Novel compound heterozygous frameshift mutations of C2orf37 in a familial Indian case of Woodhouse–Sakati syndrome

Abdulla, Mansoor C; Alazami, Anas M.; Alungal, Jemshad; Koya, Jassim M.; Musambil, Mohthash

doi:10.1007/s12041-015-0544-7

Cited by 12 publications

(11 citation statements)

References 11 publications

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“…These include three nonsense (p.S114*, p.W129*, p.W302*), five deletion [(p.A17Gfs*43, p.K90Nfs*8, p.A147Hfs*9, p.N413Tfs*21, 59–7_499del (p.?)] and four splice‐site (c.321+1T>G, c.1091+6T>G, c.1422+5G>T) mutations …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Summary Background Woodhouse–Sakati syndrome (WSS) is a rare neuroendocrine and ectodermal disorder inherited in an autosomal recessive pattern. The syndrome presents prominent clinical features, including alopecia, neuroendocrine defects, neurological findings and progressive hearing loss. The condition results from mutations in the DCAF17 gene. Aims To search for the underlying genetic defect in a Pakistani family with WSS phenotypes. Methodology Whole exome sequencing was used to search for the disease‐causing variant. Results Analysis of the exome data revealed a start loss sequence variant (c.1A>G, p.M1?) in DCAF17. Conclusion This variant is predicted to abolish translation of the DCAF17 polypeptide. To our knowledge, this is the first start loss variant identified in the DCAF17.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…As of today, 32 families with a total of 76 affected individuals have been reported, mainly from the Middle East, with a possible founder pathogenic variant c.436delC in the DCAF17 gene (S. A. Bohlega & Alkuraya, 2016). Other cases were reported from Europe, Turkey, Japan, Portugal, and the Indian sub‐continent with different pathogenic variants (Abdulla et al, 2015; Agopiantz et al, 2014; A. Alazami et al, 2010; Alazami et al, 2008; Ali et al, 2016; S. A. Bohlega & Alkuraya, 2016; Crandall et al, 1973; Devriendt et al, 1996; Gül et al, 2000; Habib et al, 2011; Koshy et al, 2008; Kurnaz et al, 2019; Louro et al, 2019; Matsuno et al, 2017; Medica et al, 2007; Sendur et al, 2019; Shah et al, 2020; Tatar et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Expanding on the phenotypic spectrum ofWoodhouse‐Sakatisyndrome due to founder pathogenic variant inDCAF17: Report of 58 additional patients from Qatar and literature review

Ali

Al‐Dewik

Mohammed

et al. 2021

American J of Med Genetics Pt A

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Woodhouse‐Sakati syndrome (WSS) is a rare autosomal recessive neuroendocrine and ectodermal disorder caused by variants in the DCAF17 gene. In Qatar, the c.436delC variant has been reported as a possible founder pathogenic variant with striking phenotypic heterogeneity. In this retrospective study, we report on the clinical and molecular characteristics of additional 58 additional Qatari patients with WSS and compare them to international counterparts' findings. A total of 58 patients with WSS from 32 consanguineous families were identified. Ectodermal and endocrine (primary hypogonadism) manifestations were the most common presentations (100%), followed by diabetes mellitus (46%) and hypothyroidism (36%). Neurological manifestations were overlapping among patients with intellectual disability (ID) being the most common (75%), followed by sensorineural hearing loss (43%) and both ID and aggressive behavior (10%). Distinctive facial features were noted in all patients and extrapyramidal manifestations were uncommon (8.6%). This study is the largest to date on Qatari patients with WSS and highlights the high incidence and clinical heterogeneity of WSS in Qatar due to a founder variant c.436delC in the DCAF17 gene. Early suspicion of WSS among Qatari patients with hypogonadism and ID, even in the absence of other manifestations, would shorten the diagnostic odyssey, guide early and appropriate management, and avoid potential complications.

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“…2 While most cases are from Saudi Arabia and the Middle East, 2,3 affected individuals from other ethnicities have been reported. [6][7][8][9][10][11] Homozygous pathogenic variants in the DCAF17 gene (formerly known as C2ORf37), allocated to chromosome 2q31.1, were discovered as the underlying cause of Woodhouse-Sakati syndrome (WSS). 3,12 The pathogenesis of the syndrome and the underlying gene remain unclear.…”

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confidence: 99%

Brain MR Imaging Findings in Woodhouse-Sakati Syndrome

Abusrair¹,

Bohlega²,

Alsemari³

et al. 2018

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Woodhouse-Sakati syndrome is a rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, and progressive extrapyramidal signs. The disease is caused by biallelic pathogenic variants in the DCAF17 gene. The purpose of this study was to describe the spectrum of brain MR imaging abnormalities in Woodhouse-Sakati syndrome. MATERIALS AND METHODS: We reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome (12 males, 14 females; age range, 16-45 years; mean age, 26.6 years). Follow-up studies were conducted for 6 patients. RESULTS: All patients had abnormal MR imaging findings. The most common abnormalities were a small pituitary gland (76.9%), pronounced basal ganglia iron deposition (73%), and white matter lesions in 69.2%. White matter lesions showed frontoparietal and periventricular predominance. All white matter lesions spared subcortical U-fibers and were nonenhanced. Prominent perivascular spaces (15.3%) and restricted diffusion in the splenium of the corpus callosum (7.6%) were less frequent findings. Follow-up studies showed expansion of white matter lesions with iron deposition further involving the red nucleus and substantia nigra. Older age was associated with a more severe degree of white matter lesions (P Ͻ .001). CONCLUSIONS: Small pituitary gland, accentuated iron deposition in the globus pallidus, and nonenhancing frontoparietal/periventricular white matter lesions were the most noted abnormalities seen in our cohort. The pattern and extent of these findings were observed to correlate with older age, reflecting a possible progressive myelin destruction and/or axonal loss. The presence of pituitary hypoplasia and white matter lesions can further distinguish Woodhouse-Sakati syndrome from other neurodegenerative diseases with brain iron accumulation subtypes. ABBREVIATIONS: NBIA ϭ neurodegenerative diseases with brain iron accumulation; WSS ϭ Woodhouse-Sakati syndrome; SNHL ϭ sensorineural hearing loss

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Novel compound heterozygous frameshift mutations of C2orf37 in a familial Indian case of Woodhouse–Sakati syndrome

Cited by 12 publications

References 11 publications

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

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

Expanding on the phenotypic spectrum ofWoodhouse‐Sakatisyndrome due to founder pathogenic variant inDCAF17: Report of 58 additional patients from Qatar and literature review

Brain MR Imaging Findings in Woodhouse-Sakati Syndrome

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