Neurologic features and genotype‐phenotype correlation in Wolfram syndrome

Chaussenot, Annabelle; Bannwarth, Sylvie; Rouzier, Cécile; Vialettes, B.; Mkadem, Samira Ait El; Chabrol, B.; Cano, Aline; Labauge, Pierre; Paquis‐Flucklinger, Véronique

doi:10.1002/ana.22160

Cited by 125 publications

(146 citation statements)

References 27 publications

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“…Onset followed this pattern: DM during the first decade of life; OA during the early second decade; DI and HD, mainly deafness, during the second decade; and UD and ND during the third decade ( Figure 1a and Supplementary Table S5 online), similar to the findings of previous publications. 29,30 Although the median age at onset of UD (n = 76) was 20 years, a large proportion of patients developed UD at 10-20 years of age, and three peaks could be observed: one at 13, the second at 21, and the third at 33 years of age. Similarly, ND (n = 67) appeared at 10-30 years of age with a median of 23 years and two peaks-one at 13, and the other at 30 years of age.…”

Section: Wolfram Syndrome Natural Historymentioning

confidence: 99%

“…The genotyping methods of Cano et al 33 and Chaussenot et al 30 were based on mutation types and differ from each other only in genotype naming. The genotyping method of Rohayem et al 34 was based on the effect of mutations on the function of WFS1.…”

Section: Genotypic Class-phenotype Correlationmentioning

confidence: 99%

“…Cano et al 33 determined that the presence of two inactivating mutations predispose to an earlier onset of DM and OA. Chaussenot et al 30 showed no association between the effect of the genotype in the neurological signs observed in patients with WS. Rohayem et al 34 showed that the age at onset of DM in patients carrying predicted complete loss of function mutations is lower than those carrying predicted partial or minor loss of function mutations.…”

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confidence: 96%

“…24 The efforts for determining WS natural history have shown the order of onset of the different clinical symptoms. 29,30 Nevertheless, the molecular complexity of WS, the wide spectrum of associated diseases, and the small size of patient cohorts (30-60 patients) complicate the establishment of reliable genotype-phenotype correlations. In all attempts, certain WFS1 mutations were associated with milder or with more severe phenotypes.…”

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confidence: 99%

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Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Heredia

Clèries

Nunes

2013

Genetics in Medicine

137

223

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Section: Wolfram Syndrome Natural Historymentioning

confidence: 99%

Section: Genotypic Class-phenotype Correlationmentioning

confidence: 99%

mentioning

confidence: 96%

mentioning

confidence: 99%

See 2 more Smart Citations

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Heredia

Clèries

Nunes

2013

Genetics in Medicine

137

223

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“…This is an autosomal dominant disorder caused by heterozygous variants in WFS1, resulting in sensorineural hearing loss, DM, psychiatric illness and variable optic atrophy within the first decade of life. 10,11 1.6 Analytical methods Bi-directional fluorescent Sanger sequencing of coding and intronexon boundaries of WFS1 is the mainstay analytical method as an initial analysis. CISD2 screening can be performed if WFS2 is suspected, as this is rare.…”

Section: Mutational Spectrummentioning

confidence: 99%

Clinical utility gene card for: Wolfram syndrome

et al. 2016

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Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

et al. 2014

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he diagnostic evaluation of a patient with chronic progressive cerebellar ataxia is clinically challenging. Cerebellar ataxia is associated with a heterogeneous array of neurologic conditions spanning common acquired etiologies to rare genetic disorders present only in single families. [1][2][3][4][5] Currently, more than 60 distinct neurogenetic conditions are known to cause primary cerebellar ataxia. In most cases, it is difficult to differentiate these disorders owing to phenotype variability within a disorder and overlap between disorders. [1][2][3][4][5] Further complicating matters, there are nearly 300 additional genetic conditions that can include cerebellar ataxia as a clinical finding. 6 Many patients present to clinicians with lateonset symptoms and no reported family history 7 and, in the absence of other identifying etiologies, the role of genetic disease in this population is not well understood. 1,3,5 The availability of next-generation clinical exome sequencing (CES) has made it possible to perform genomewide genetic evaluations for patients as part of a detailed clinical workup. 8,9 This is a potentially useful addition to the physician's armamentarium because, given the number of rare genes related to ataxia, overuse of low-yield single-gene and genetic panel testing represents a significant cost to patient health care. 7,10 The anticipated widespread benefits of CES have already prompted recommendations for its inclusion as part of routine clinical algorithms. 4,5,9,11,12 Although CES is much less expensive than sequentially examining mul-IMPORTANCE Cerebellar ataxias are a diverse collection of neurologic disorders with causes ranging from common acquired etiologies to rare genetic conditions. Numerous genetic disorders have been associated with chronic progressive ataxia and this consequently presents a diagnostic challenge for the clinician regarding how to approach and prioritize genetic testing in patients with such clinically heterogeneous phenotypes. Additionally, while the value of genetic testing in early-onset and/or familial cases seems clear, many patients with ataxia present sporadically with adult onset of symptoms and the contribution of genetic variation to the phenotype of these patients has not yet been established.OBJECTIVE To investigate the contribution of genetic disease in a population of patients with predominantly adult-and sporadic-onset cerebellar ataxia. DESIGN, SETTING, AND PARTICIPANTSWe examined a consecutive series of 76 patients presenting to a tertiary referral center for evaluation of chronic progressive cerebellar ataxia. MAIN OUTCOMES AND MEASURESNext-generation exome sequencing coupled with comprehensive bioinformatic analysis, phenotypic analysis, and clinical correlation. RESULTSWe identified clinically relevant genetic information in more than 60% of patients studied (n = 46), including diagnostic pathogenic gene variants in 21% (n = 16), a notable yield given the diverse genetics and clinical heterogeneity of the cerebellar ataxias. CONCLUSIONS AND RELE...

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Neurologic features and genotype‐phenotype correlation in Wolfram syndrome

Abstract: This series concerns the largest cohort of WS patients reported to date. It illustrates the wide variety of neurologic signs in this syndrome and the necessity of rapid therapeutic coverage to improve the prognosis.

Cited by 125 publications

References 27 publications

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Clinical utility gene card for: Wolfram syndrome

Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia

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