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      Phenotypic Variability of c.436delC DCAF17 Gene Mutation in Woodhouse-Sakati Syndrome


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          Case series

          Patients: 38, female • 28, female • 41, female • 18, female • 23, male

          Final Diagnosis: Woodhouse-Sakati syndrome

          Symptoms: Hypogonadism • dystonia • alopecia • hearing loss • diabetes

          Medication: —

          Clinical Procedure: —

          Specialty: Endocrinology and Metabolic


          Rare disease


          Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive genetic condition that was first described in 1983. Since its original description, approximately 50 cases have been reported with various clinical signs and symptoms. Characteristics include progressive neurologic deterioration with extrapyramidal involvement and polyendocrinopathy most notable for hypogonadism starting in early adolescence. Clinical presentation is variable, and a subset of patients may have additional features, such as premature aging, alopecia, distinctive facial features, cognitive impairment, or deafness.

          Case Report:

          We illustrate the phenotypic variability of 5 patients with WSS due to the previously reported homozygous single nucleotide deletion c.436delC in the DCAF17 gene, identified in 2008. Despite identical genetic alteration, our 5 patients had various clinical features among them and compared with previously reported cases with the same pathogenic mutation.


          The phenotypic variability of WSS due to c.436delC founder mutation may have a wider range than previously recognized.

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          Most cited references16

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          Mutations in C2orf37, encoding a nucleolar protein, cause hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome.

          Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (also referenced as Woodhouse-Sakati syndrome) is a rare autosomal recessive multisystemic disorder. We have identified a founder mutation consisting of a single base-pair deletion in C2orf37 in eight families of Saudi origin. Three other loss-of-function mutations were subsequently discovered in patients of different ethnicities. The gene encodes a nucleolar protein of unknown function, and the cellular phenotype observed in patient lymphoblasts implicates a role for the nucleolus in the pathogenesis of this disease. Our findings expand the list of human disorders linked to the nucleolus and further highlight the developmental and/or maintenance functions of this organelle.
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            A syndrome of hypogonadism, alopecia, diabetes mellitus, mental retardation, deafness, and ECG abnormalities.

            A distinct and previously undescribed syndrome has been observed in six Saudi Arabian patients from two highly inbred families. The parents were normal, indicating an autosomal recessive pattern of inheritance. All the patients have a distinctive facial appearance, hypogonadism, sparse or absent hair, diabetes mellitus, mental retardation, mild deafness, and variable S-T and T wave abnormalities on the electrocardiograph.
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              Phenotypic heterogeneity in Woodhouse-Sakati syndrome: two new families with a mutation in the C2orf37 gene.

              Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome [also known as Woodhouse-Sakati syndrome (WSS)] is a rare autosomal recessive neuroendocrine and ectodermal disorder. The syndrome was first described by Woodhouse and Sakati in 1983, and 47 patients from 23 families have been reported so far. We report on an additional seven patients (four males and three females) from two highly consanguineous Arab families from Qatar, presenting with a milder phenotype of WSS. These patients show the spectrum of clinical features previously found in WSS, but lack evidence of diabetes mellitus and extrapyramidal symptoms. These two new families further illustrate the natural course and the interfamilial phenotypic variability of WSS that may lead to challenges in making the diagnosis. In addition, our study suggests that WSS may not be as infrequent in the Arab world as previously thought.

                Author and article information

                Am J Case Rep
                Am J Case Rep
                The American Journal of Case Reports
                International Scientific Literature, Inc.
                25 March 2018
                : 19
                : 347-353
                [1 ]Department of Internal Medicine, St. Elizabeth’s Medical Center, Boston, MA, U.S.A.
                [2 ]Department of Clinical Genomics, Mayo Clinic, Rochester, MN, U.S.A.
                [3 ]Department of Neurology, Mayo Clinic, Rochester, MN, U.S.A.
                Author notes

                Authors’ Contribution:


                Study Design


                Data Collection


                Statistical Analysis


                Data Interpretation


                Manuscript Preparation


                Literature Search


                Funds Collection

                Conflict of interest: None declared

                Corresponding Author: Ralitza H. Gavrilova, e-mail gavrilova.ralitza@ 123456mayo.edu
                © Am J Case Rep, 2018

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)


                alopecia,dystonic disorders,hypogonadism,leukoencephalopathies


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