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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.

SUBMITTER: Zhou M

PROVIDER: S-EPMC8734028 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Case Report: A Deletion Variant in the <i>DCAF17</i> Gene Underlying Woodhouse-Sakati Syndrome in a Chinese Consanguineous Family.

Project description:Woodhouse-Sakati syndrome (WSS, MIM 241080) is a rare neuroendocrine disease characterized by hair loss, hypogonadism, diabetes, hearing loss, and extrapyramidal syndrome, and is usually caused by mutations in the DCAF17 gene as an inherited disease. DCAF17 plays an important role in mammalian gonadal development and infertility. So far, there have been no WSS reports in China. The patient introduced in this case is from a consanguineous family. The main symptoms of the patient were alopecia and gonadal agenesis. Other symptoms such as hearing loss, intellectual disability, and hyperglycemia were remarkable, and these symptoms are often observed in WSS patients. We found a nonsense mutation in the 11th exon of the gene DCAF17 (Refseq: NM_025000) in the patient and her younger brother, which confirmed the diagnosis of WSS. The genetic results also showed that the mutation was inherited from their healthy first-cousin parents.

| S-EPMC8498701 | biostudies-literature

Woodhouse-Sakati Syndrome: Report of the First Tunisian Family with the C2orf37 Gene Mutation.

Project description: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.

| S-EPMC4886203 | biostudies-other

Novel splicing-site mutation in DCAF17 gene causing Woodhouse-Sakati syndrome in a large consanguineous family.

Project description:BackgroundWoodhouse-Sakati syndrome is a rare autosomal recessive disease with endocrine and neuroectodermal aberrations with heterogeneous phenotypes and disease course. The most common phenotypes of the disease are progressive sensorineural hearing loss and alopecia, mild-to-moderate mental retardation and hypogonadism. The disease results from mutations in the DCAF17 gene.MethodHere, we reported a large consanguineous pedigree with multiple affected individuals with Woodhouse-Sakati syndrome phenotypes. Laboratory tests confirmed the endocrine perturbance in affected individuals. To find out the underlying genetic change, whole-exome sequencing was carried out.ResultAnalysis of the exome data identified a splicing-site deletion NM_025000.3:c.1423-1_1425delGACA in DCAF17 gene. Sanger sequencing confirmed the co-segregation of the variant with the disease phenotypes in the family.ConclusionThe variant is predicted to cause aberrant splicing, i.e., exon skipping, resulting in the translation of a truncated functionless protein which results in appearance of typical phenotypic features and clinical laboratory findings of Woodhouse-Sakati syndrome in affected members of the family.

| S-EPMC8761431 | biostudies-literature

Brain MR Imaging Findings in Woodhouse-Sakati Syndrome.

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| S-EPMC7655421 | biostudies-literature

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

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| S-EPMC5881453 | biostudies-other

Phenotypic heterogeneity in Woodhouse-Sakati syndrome: two new families with a mutation in the C2orf37 gene.

Project description: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.

| S-EPMC6905109 | biostudies-literature

Hepatocyte nuclear factor 1B mutation in a Chinese family with renal cysts and diabetes syndrome: A case report.

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| S-EPMC8554446 | biostudies-literature

Novel deletion mutation in a Chinese family with X-linked alport syndrome.

Project description:BACKGROUNDS AND OBJECTIVES:alport syndrome (AS) is a progressive hereditary condition that is characterized by haematuria, proteinuria, progressive renal impairment, and end stage kidney disease (ESRD). Approximately 85% of AS patients have X-linked mutations in the COL4A5 gene that encodes type IV collagen. The aim of our study was to identify the gene responsible for glomerulopathy in a 3-generation Chinese pedigree with familial haematuria. METHODS:We examined five members of a Chinese family clinically suspected of X-linked AS caused by COL4A5 gene mutations. All 51 exons of the COL4A5 gene were screened by direct DNA sequencing. RESULTS:We identified the novel deletion mutation c. 3990_4016delCCC…TCC in COL4A5 in three affected individuals with haematuria, but the mutation was absent in the other 2 healthy family members and 100 unrelated healthy controls. CONCLUSIONS:Our result demonstrates that the mutation is pathogenic and novel and has meaningful implications for the diagnosis and genetic counselling of cases with AS. The results in the study broaden the genotypic spectrum of known mutations for AS.

| S-EPMC6962970 | biostudies-literature

Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus.

Project description:Neonatal diabetes is a highly genetically heterogeneous disorder. There are over 20 distinct syndromic and non-syndromic forms, including dominant, recessive and X-linked subtypes. Biallelic truncating or mis-sense mutations in the DNA-binding domain of the RFX6 transcription factor cause an autosomal recessive, syndromic form of neonatal diabetes previously described as Mitchell-Riley syndrome. In all, eight cases have been reported, with the age at onset of diabetes in the first 2 weeks of life. Here we report two individuals born to double first cousins in whom intestinal atresias consistent with a diagnosis of Mitchell-Riley syndrome were diagnosed at birth, but in whom diabetes did not present until the ages of 3 and 6 years. Novel compound heterozygous RFX6 nonsense mutations (p.Arg726X/p.Arg866X) were identified at the 3' end of the gene. The later onset of diabetes in these patients may be due to incomplete inactivation of RFX6. Genetic testing for RFX6 mutations should be considered in patients presenting with intestinal atresias in the absence of neonatal diabetes.

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Iranian neonatal diabetes mellitus due to mutation in PDX1 gene: a case report.

Project description:BACKGROUND:Neonatal diabetes mellitus with hyperglycemia during the first 6?months of life is a rare disorder that can occur in all races and societies. CASE PRESENTATION:In this study, we introduced an Iranian (Persian) 65-day-old patient with neonatal diabetes mellitus with novel homozygous mutation in the pancreatic and duodenal homeobox 1, PDX1, gene, which is also known as IPF1 gene, located in exon 2. This case was a newborn boy born in Vali-Asr Hospital, Tehran; he was diagnosed as having hyperglycemia on 28th day. Genetic analysis detected a homozygous mutation on PDX1 gene on chromosome 13. It is a novel homozygous mutation in the PDX1 gene (NM_000209.3), p.Phe167Val. This mutation was confirmed by Sanger sequencing. There was no evidence of agenesis of the pancreas. CONCLUSIONS:We reported a case of neonatal diabetes mellitus due to novel homozygous mutation in the PDX1 gene without exocrine pancreas manifestations.

| S-EPMC6670147 | biostudies-literature

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