Genetic analysis of 2299delG and C759F mutations (USH2A) in patients with visual and/or auditory impairments

Aller, Elena; Nájera, Carmén; Millán, José María; Oltra, Silvestre; Pérez-Garrigues, Herminio; Vilela, Concepción; Navea, Amparo; Beneyto, Magdalena

doi:10.1038/sj.ejhg.5201138

Cited by 54 publications

(44 citation statements)

References 9 publications

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“…[34][35][36][37][38] The genotyping presented here revealed a second common mutation, c.11864G.A (p.W3955X) in exon 61 of this gene. This nonsense mutation truncates the long isoform of the USH2A protein.…”

Section: Evaluation Of the Usher Genotyping Microarraymentioning

confidence: 65%

Development of a genotyping microarray for Usher syndrome

Cremers

Kimberling

Külm

et al. 2006

Journal of Medical Genetics

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Background: Usher syndrome, a combination of retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction, displays a high degree of clinical and genetic heterogeneity. Three clinical subtypes can be distinguished, based on the age of onset and severity of the hearing impairment, and the presence or absence of vestibular abnormalities. Thus far, eight genes have been implicated in the syndrome, together comprising 347 protein-coding exons. Methods: To improve DNA diagnostics for patients with Usher syndrome, we developed a genotyping microarray based on the arrayed primer extension (APEX) method. Allele-specific oligonucleotides corresponding to all 298 Usher syndrome-associated sequence variants known to date, 76 of which are novel, were arrayed. Results: Approximately half of these variants were validated using original patient DNAs, which yielded an accuracy of > 98%. The efficiency of the Usher genotyping microarray was tested using DNAs from 370 unrelated European and American patients with Usher syndrome. Sequence variants were identified in 64/140 (46%) patients with Usher syndrome type I, 45/189 (24%) patients with Usher syndrome type II, 6/21 (29%) patients with Usher syndrome type III and 6/20 (30%) patients with atypical Usher syndrome. The chip also identified two novel sequence variants, c.400C > T (p.R134X) in PCDH15 and c.1606T > C (p.C536S) in USH2A. Conclusion: The Usher genotyping microarray is a versatile and affordable screening tool for Usher syndrome. Its efficiency will improve with the addition of novel sequence variants with minimal extra costs, making it a very useful first-pass screening tool

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Section: Evaluation Of the Usher Genotyping Microarraymentioning

confidence: 65%

Development of a genotyping microarray for Usher syndrome

Cremers

Kimberling

Külm

et al. 2006

Journal of Medical Genetics

View full text Add to dashboard Cite

show abstract

“…Since the identification of the USH2A gene (Eudy et al, 1998) several research groups have scanned the USH2A gene in USH2 patients from various ethnic backgrounds (Eudy et al, 1998;Liu et al, 1999;Adato et al, 2000;Dreyer et al, 2000;Rivolta et al, 2000;Weston et al, 2000;Leroy et al, 2001;Najera et al, 2002;Bernal et al, 2003;Aller et al, 2004;Ouyang et al, 2004;Pennings et al, 2004;Seyedahmadi et al, 2004;Maubaret et al, 2005;Aller et al, 2006;Cremers et al, 2007;Kaiserman et al, 2007;Baux et al, 2007). Such investigations are a prerequisite in order to provide an accurate and unambiguous molecular diagnosis for patients with Usher syndrome type II.…”

Section: Discussionmentioning

confidence: 99%

Spectrum of USH2A mutations in Scandinavian patients with Usher syndrome type II

et al. 2008

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Usher syndrome type II (USH2) is an autosomal recessive disorder, characterised by moderate to severe high-frequency hearing impairment, normal balance function and progressive visual impairment due to retinitis pigmentosa. Usher syndrome type IIa, the most common subtype, is defined by mutations in the USH2A gene encoding a short and a recently discovered long usherin isoform comprising 21 and 73 exons, respectively. More than 120 different disease-causing mutations have been reported, however, most of the previous reports concern mutations restricted to exons 1-21 of the USH2A gene. To explore the spectrum of USH2A disease-causing mutations among Scandinavian USH2 cases, patients from 118 unrelated families of which 27 previously had been found to carry mutations in exons 1-21 were subjected to extensive DNA sequence analysis of the full size USH2A gene. Altogether, 122 USH2A DNA sequence alterations were identified of which 57 were predicted to be disease-causing, 7 were considered to be of uncertain pathogenicity and 58 were predicted to be benign variants. Of 36 novel pathogenic USH2A mutations 31 were located in exons 22-73, specific to the long isoform. USH2A mutations were identified in 89/118 (75.4%) families. In 79/89 (88.8%) of these families two pathogenic mutations were identified whereas in 10/89 (11.2%) families the second mutation remained unidentified. In 5/118 (4.2%) families the USH phenotype could be explained by mutations in the USH3A gene. The results presented here provide a comprehensive picture of the genetic aetiology of Usher syndrome type IIA in Scandinavia as it is known to date.

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“…9 10 In addition, this gene has been shown to be responsible for some recessive cases of non-syndromic retinitis pigmentosa. [10][11][12] The USH2A gene located in 1q41 13 was first described as comprising 21 exons that expanded 259 kb of genomic DNA. The encoded protein was predicted to consist of 1546 amino acids containing laminin epidermal growth factor and fibronectin type III motifs, typical of extracellular matrix proteins.…”

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confidence: 99%