Wolfram syndrome and WFS1 gene

Rigoli, Luciana; Lombardo, Fortunato; Bella, Chiara Di

doi:10.1111/j.1399-0004.2010.01522.x

Cited by 130 publications

(127 citation statements)

References 115 publications

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“…Other complications include urogenital anomalies, and less frequent complications such as gastrointestinal anomalies, most often dysmotility and/or chronic diarrhoea. Primary gonadal atrophy is common in males, and many females have menstrual irregularity and delayed menarche [2,3]. Follow-up studies demonstrate that WS patients could develop all symptoms if they live long enough.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Novel Wsf1 Mutations in a Sicilian Child with Wolfram Syndrome

Pizzolanti¹

2014

J Genet Syndr Gene Ther

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Wolfram Syndrome (WS) is a rare hereditary disease with autosomal recessive inheritance with incomplete penetrance. It is characterized by diabetes mellitus associated with progressive optic atrophy. The diagnosis is essentially clinical and mutation analysis is used to confirm the diagnosis. In the present study we describe the clinical and molecular features of a diabetic child carrying two novel WFS1 mutations. The Sicilian proband and his non-affected family were studied. Ophthalmologic examination included: visual acuity determination and funduscopy, optical coherent tomography, retinal fluorangiography, perimetry and electroretinogram. Molecular methods: automatic sequencing of PCR amplified WFS1 gene fragments and qRT-PCR analysis of WFS1 transcripts. 3 WSF1 mutations have been identified in the proband. One allele carries 2 paternally inherited mutations (c.1332 C>G and c.1631C>G) in exon-8, never annotated before, in heterozygosis with one "de novo" classic mutation (c.505 G>A) in exon-5. In addition, we report an unexpected molecular feature: higher WFS1 mRNA levels in the proband compared to the father. Milan, Italy) following manifacturer's instructions. A neuroblastoma cell line (LAN5) used as a positive control. WFS1 expression was analysed by real-time quantitative RT-PCR (qRT-PCR) in individual samples and WFS1 mRNA levels were quantified in comparison to β-actin mRNA expression. WFS1 PCR primers were purchased from Quiagen (Quantitect Primer Hs_WFS1_1_SG QT00082663) the amplicon size was 117 bp (Suppl. Figure 1); β-actin primers were obtained from RealTimePrimers.com (Elkins Park, PA, USA) with the following sequences: F 5'-GGACTTCGAGCAAGAGATGG-3'; R 5'-AGCACTGTGTTGGCGTACAG-3'; the amplicon size was 234 bp. All reactions were performed using the LightCycler 1.0 (Roche Diagnostics GMbH, Germany). Briefly, 2 g of total RNA was retrotranscribed using the ImProm-II™ Reverse Transcription System (Promega, Milan, Italy). Each RNA was combined with 1l of oligo16dT (Promega Milan, Italy) and thermally denatured at 70°C for 5 minutes and then chilled on ice. As a final step, the template-oligodT combination was added to the reaction mix (4 l ImProm-II™ 1X Reaction Buffer, 1l ImProm-II™ Reverse Transcriptase, 3.2 l Magnesium Chloride 3 mM, 1 l dNTPs mix 10 mM and 1 l Recombinant RNasin Ribonuclease Inhibitor 1u/l) and nuclease-free water was added to 20 l of final volume on ice. Following an initial annealing at 25°C for 5 minutes, the reaction was incubated at 42°C for one hour. In order to heat-inactivate the ImProm-II Reverse Transcriptase the reaction mix was finally incubated at 70°C for 15 minutes. Journal of Genetic Syndromes & Gene TherapyReal-time PCR was performed using 2 l of cDNA diluited 1:5, plus 10 l of Quantitech master mix (Qiagen), 2 l of Quantitect Primer Hs_WFS1_1_SG or β-actin primers, and nuclease-free water to 20 l of final volume. A standard reference curve was performed in parallel using RNAs extracted from LAN5 cell line serially 1:2 diluited starting from 100 ng reaction...

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Section: Introductionmentioning

confidence: 99%

“…The WFS1 gene transcribes a 3.6 kb mRNA that encodes Wolframin, a 890-amino-acid protein, abundantly detected in the adult human heart, brain, placenta, lung, and pancreas beta-cells [3,5,6]. Wolframin is a calmodulin glycoprotein resident in the membrane of the Endoplasmic Reticulum (ER) involved in the ER stress signalling [3,13].…”

Section: Introductionmentioning

confidence: 99%

Identification of Novel Wsf1 Mutations in a Sicilian Child with Wolfram Syndrome

Pizzolanti¹

2014

J Genet Syndr Gene Ther

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“…19 The induction of ER stress in the lens during development has been shown to cause apoptotic cell death in lens epithelial cells, 20 suggesting that the lens would be at risk with defective Wolframin function. Our experiment shows this protein is highly expressed in the developing lens ( Figure 3) and likely to be involved in membrane trafficking.…”

Section: Discussionmentioning

confidence: 99%

Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans

et al. 2013

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“…4 We draw attention to the fact that the WFS1 gene is also located in this region and determines the Wolfram syndrome (WS, OMIM 2223000), 1 which is an autosomal recessive condition also referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness). 6,7 Occurrences of diabetes mellitus and optic atrophy together is sufficient for diagnosing WS. 6,7 However, until the latest assessment of our patient, at the age of 22 years, only the DM was observed, which would be not expected for a patient with WS (usually, patients with WS present optic atrophy before the age of 19 years).…”

Section: 4mentioning

confidence: 99%

“…6,7 Occurrences of diabetes mellitus and optic atrophy together is sufficient for diagnosing WS. 6,7 However, until the latest assessment of our patient, at the age of 22 years, only the DM was observed, which would be not expected for a patient with WS (usually, patients with WS present optic atrophy before the age of 19 years). of all cases of diabetes, and susceptibility to this is considered to be largely inherited, residing especially in the HLA genotypes DR and DQ.…”

Section: 4mentioning

confidence: 99%

Type 1 diabetes in a patient with Ellis-van Creveld syndrome

Graziadio

Bernardi²,

Rosa³

et al. 2012

Sao Paulo Med. J.

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CONTEXT: Ellis-van Creveld (EVC) syndrome is a rare autosomal recessive disease characterized by disproportionate short stature, narrow thorax, postaxial polydactyly, nail and tooth abnormalities and congenital heart disease. CASE REPORT: The patient was a 22-year-old Caucasian man, the third child of consanguineous parents. He received the diagnosis of insulin-dependent diabetes mellitus (DM) at 16 years of age, and around one year later, he underwent surgery to correct a partial atrioventricular septal defect. Upon physical examination, at 22 years of age, he presented stature of 145.5 cm (P3), weight of 49 kg (P3), head circumference of 54 cm (P2-50), high palate, absence of one of the lower lateral incisor teeth, narrow shoulders, narrowing of the upper thorax, scoliosis, rhizomelic shortening of the upper limbs, brachydactyly, postaxial polydactyly and clinodactyly of the second and third fingers. The lower limbs showed rhizomelic shortening with significant genu valgum (knock-knee deformity), small feet with postaxial polydactyly, syndactyly between the second and third toes and hallux valgus. Multiple melanocytic nevi were evident on the face, thorax and limbs. At that time, he was using neutral protamine Hagedorn (NPH) insulin, with poorly controlled DM. The clinical findings presented led to the diagnosis of EVC syndrome. Only one case of this syndrome has been described with DM so far. Attention is drawn to the fact that the genes associated with this syndrome are located close to those of the Wolfram syndrome, a condition that leads to early-onset diabetes.resUMo CONTEXTO: A síndrome de Ellis-van Creveld (EVC) é uma doença autossômica recessiva rara, caracterizada por baixa estatura desproporcionada, tórax estreito, polidactilia pós-axial, anormalidades em unhas e dentes e cardiopatia congênita. RELATO DO CASO: O paciente é um rapaz caucasiano de 22 anos, o terceiro filho de pais consanguíneos. Recebeu diagnóstico de diabetes melito (DM) insulino-dependente aos 16 anos, sendo que, cerca de um ano depois, foi submetido a cirurgia cardíaca de correção de defeito de septo atrioventricular parcial. Ao exame físico, aos 22 anos, ele apresentava estatura de 145,5 cm (P3), peso de 49 kg (P3), perímetro cefálico de 54 cm (P2-50), palato alto, ausência de um dos dentes incisivos inferiores laterais, ombros estreitos, estreitamento do tórax superior, escoliose, encurtamento rizomélico dos membros superiores, braquidactilia, polidactilia pós-axial e clinodactilia dos segundo e terceiro dedos. Nos membros inferiores, observava-se encurtamento rizomélico com importante geno valgo (deformidade dos joelhos-batidos), pés pequenos com polidactlia pós-axial, sindactilia entre segundo e terceiro dedos, e háluces valgos. Múl-tiplos nevos melanocíticos eram evidentes na face, tórax e membros. Neste momento ele está em uso de insulina NPH (neutral protamine Hagedorn), com um controle inadequado do DM. Seus achados clínicos levaram ao diagnóstico de síndrome de EVC. Apenas um caso desta síndrome foi descrito com DM ...

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Wolfram syndrome and WFS1 gene

Cited by 130 publications

References 115 publications

Identification of Novel Wsf1 Mutations in a Sicilian Child with Wolfram Syndrome

Identification of Novel Wsf1 Mutations in a Sicilian Child with Wolfram Syndrome

Wolfram gene (WFS1) mutation causes autosomal dominant congenital nuclear cataract in humans

Type 1 diabetes in a patient with Ellis-van Creveld syndrome

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