title: Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati syndrome.
abstract: Woodhouse Sakati syndrome (WSS, MIM 241080) is a rare autosomal recessive genetic condition characterized by alopecia, hypogonadism, hearing impairment, diabetes mellitus, learning disabilities and extrapydamidal manifestations. Sequence variants in the gene DCAF17, encoding nucleolar substrate receptor, were identified as the underlying cause of inherited WSS. Considerable phenotypic heterogeneity exists in WSS with regard to severity, organs involvement and age of onset, both in inter-familial and intra-familial cases. In this study, the genetic characterization of a consanguineous pedigree showing mild features of WSS was performed, followed by structural analysis of truncated protein. Exome sequencing identified a novel single base deletion variant (c.270delA; K90Nfs8*) in third exon of the gene DCAF17 (RefSeq; NM_025000), resulting in a truncated protein. Structural analysis of truncated DCAF17 revealed absence of amino acid residues crucial for interaction with DDB1. Taken together, the data confirmed the single base pair deletion as the underlying cause of this second report of WSS from Pakistan. This signifies the vital yet unexplored role of DCAF17 both in development and maintenance of adult tissues homeostasis.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.|Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: R H
authors.initials: RH
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: K
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Mardan, Pakistan.
authors.forename: A
authors.initials: A
authors.lastname: Nasir
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: W
authors.initials: W
authors.lastname: Steyaert
authors.affiliation: Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium.
authors.forename: P J
authors.initials: PJ
authors.lastname: Coucke
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: W
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000235:genetics* / Q000503:physiopathology; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000503:physiopathology; D001480:Basal Ganglia Diseases / Q000235:genetics* / Q000503:physiopathology; D003241:Consanguinity; D003920:Diabetes Mellitus / Q000235:genetics* / Q000503:physiopathology; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D007006:Hypogonadism / Q000235:genetics* / Q000503:physiopathology; D008607:Intellectual Disability / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010154:Pakistan; D010375:Pedigree; D017384:Sequence Deletion / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics*
chemical_list: C556016:DCAF17 protein, human; D009687:Nuclear Proteins; D043743:Ubiquitin-Protein Ligase Complexes
keywords: CUL4-DDB1; DCAF17; IGF-1; Woodhouse Sakati syndrome; alopecia; hypogonadism