Identification of unsuspected Wolfram syndrome cases through clinical assessment and WFS1 gene screening in type 1 diabetes mellitus patients

Blanco-Aguirre, Maria E.; Parra, David Rivera-De la; Tapia-Garcia, Hugo; Gonzalez-Rodriguez, Johanna; Welskin, Daniela; Arroyo-Yllanes, María Estela; Escudero, Irineo; Núñez-Hernández, Jorge A.; Medina-Bravo, Patricia; Zenteno, Juan Carlos

doi:10.1016/j.gene.2015.04.040

Cited by 17 publications

(17 citation statements)

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“…Urinary tract abnormalities and high output of urine are associated with the development of diabetes mellitus and diabetes insipidus which contribute to renal tract dilation (Page et al, 1976). Additionally, all the selected patients showed audiographic defects and neurological deterioration which is consistent with previous studies (Hardy et al, 1999, Gasparin et al, 2009, Blanco-Aguirre et al, 2015). …”

Section: Discussionsupporting

confidence: 91%

“…Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder, characterized by the manifestation of multisystem symptoms at an early age of life (Blanco-Aguirre et al, 2015). Several studies have previously described the linkage of this syndrome to certain markers at chromosome 4p16.1 and specifically the gene WFS1 was identified as the causative agent in the pathophysiology of Wolfram syndrome (Polymeropoulos et al, 1994, Barrientos et al, 1996, Collier et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

“…WS is also known by the acronym DIDMOAD given that it is characterized by the presentation of multisystem symptoms: diabetes insipidus (DI), type I diabetes mellitus (DM), optic atrophy (OA), and deafness (D) (Blanco-Aguirre et al, 2015). Other clinical symptoms were found to be associated with WS including ataxia, peripheral neuropathy, psychiatric problems, and renal tract abnormalities (Haghighi et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, these mutations were found to be mostly distributed in exon 8 and they include missense, nonsense, splicing mutations, frameshift insertions, and frameshift deletions, with homozygous and compound heterozygous genotypes (Chaussenot et al, 2011). Most of the mutations found in WS patients result in the expression of a loss of function wolframin; however, the specific role of the mutated wolframin in the expression of WS symptoms and the exact genotype-phenotype relationship in WS patients are not clear yet (Blanco-Aguirre et al, 2015). …”

Section: Introductionmentioning

confidence: 99%

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Identification of a novel WFS1 homozygous nonsense mutation in Jordanian children with Wolfram syndrome

et al. 2016

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Wolfram syndrome (WS) is a rare autosomal recessive neurodegenerative disorder characterized by the presentation of early onset type I diabetes mellitus and optic atrophy with later onset diabetes insipidus and deafness. WFS1 gene was identified on chromosome 4p16.1 as the gene responsible for WS disease given that most of the WS patients were found to carry mutations in this gene. This study was carried out to investigate the molecular spectrum of WFS1 gene in Jordanian families. Molecular and clinical characterization was performed on five WS patients from two unrelated Jordanian families. Our data indicated that WS patients of the first family harbored two deletion mutations (V415del and F247fs) located in exon 8 and exon 7 respectively, with a compound heterozygous pattern of inheritance; while in the second family, we identified a novel nonsense mutation (W185X) located in exon 5 in the N-terminal cytoplasmic domain with a homozygous pattern of inheritance. This mutation can be considered as loss of function mutation since the resulting truncated protein lost both the transmembrane domain and the C-terminal domain. Additionally, the W185X mutation lies within the CaM binding domain in wolframin protein which is thought to have a role in the regulation of wolframin function in response to calcium levels.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of a novel WFS1 homozygous nonsense mutation in Jordanian children with Wolfram syndrome

et al. 2016

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“…Hasta la fecha no existe ninguna intervención que altere la progresión de la enfermedad o prolongue la expectativa de vida en el SW, pero el reconocimiento temprano de este síndro-me y sus complicaciones puede incrementar la calidad de vida de quienes la padecen al permitir intervenciones tempranas para los componentes de este síndrome 22 . Aunque el SW es una enfermedad rara, deberá sospecharse en todos aquellos casos de diabetes mellitus con síntomas de atrofia óptica progresiva, pérdida auditiva, diabetes insípida, síntomas psiquiá-tricos o alteraciones del tracto urinario 43,61 .…”

Section: Discussionunclassified