A Mutation (2314delG) in the Usher Syndrome Type IIA Gene: High Prevalence and Phenotypic Variation

Liu, Xuezhong; Hope, Carolyn; Liang, Chuan Yu; Zou, Jiu Mu; Xu, Li Rong; Cole, Trevor; Mueller, Robert F.; Bundey, Sarah; Nance, Walter E.; Steel, Karen P.; Brown, Steve

doi:10.1086/302332

Cited by 78 publications

(89 citation statements)

References 12 publications

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“…A wide range of phenotypes in patients with Usherin mutations have been described; there have even been reports on cases carrying the same mutations associated with different clinical signs: homozygosity for C759F has been described in nonsyndromic RP cases (Rivolta et al, 8 present report) and in asymptomatic cases; 9 homozygosity for 2299delG has been described in two monozygotic twins, one of them suffering the typical USHII syndrome and the other one suffering the atypical USH syndrome; 6 compound heterozygotes C759F/2299delG have been described as nonsyndromic RP, 8 and as atypical USH syndrome (present report). These findings may indicate that the nature of the mutations along with other genetic or environmental factors are involved in the phenotype of the USH2A gene mutations.…”

Section: Right Earmentioning

confidence: 86%

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

Aller

Nájera

Millán³

et al. 2004

Eur J Hum Genet

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The most common mutation in the USH2A gene (Usherin), 2299delG, causes both typical Usher (USH) syndrome type II and atypical USH syndrome, two autosomal recessive disorders, characterised by moderate to severe sensorineural hearing loss and retinitis pigmentosa (RP). Furthermore, the C759F mutation in the USH2A gene has been described in 4.5% of patients with nonsyndromic recessive RP. We have investigated the presence of the 2299delG and/or the C759F mutations in 191 unrelated Spanish patients with different syndromic and nonsyndromic retinal diseases, or with nonsyndromic hearing impairment. The 2299delG mutation was observed in patients with clinical signs of USHII or of atypical USH syndrome, whereas the C759F mutation, regardless of being associated with the 2299delG mutation or not, was identified in cases with nonsyndromic RP, as well as in patients with RP associated with a variability of hearing impairment. The comparative analysis of both phenotypic and genotypic data supports the hypothesis that sensorineural hearing loss in patients with RP may depend on the nature and on the association of the USH2A allele variants present.

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Section: Right Earmentioning

confidence: 86%

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

Aller

Nájera

Millán³

et al. 2004

Eur J Hum Genet

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“…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%

“…USH2A mutations have also been detected in patients with an atypical USH2 phenotype characterised by progressive hearing loss, variable vestibular dysfunction and RP (Liu et al, 1999). Furthermore, putative pathogenic USH2A mutations have been identified in patients with nonsyndromic recessive RP and homozygously in two asymptomatic individuals (Rivolta et al, 2000;Bernal et al, 2003).…”

Section: Introductionmentioning

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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“…The allele frequency distribution of c.2299delG varies geographically in Europe. This mutation accounts for 47.5% of USH2A alleles in Denmark and for 36% in Scandinavia, 2 whereas an allelic frequency of 31% was found in the Netherlands, 15 16-36 % in the United Kingdom, 16,17 15% in Spain 10 and 10% in France (unpublished results). A common ancestral origin has been hypothesised for the c.2299delG mutation on the basis that alleles bearing the c.2299delG mutation share the same core haplotype, restricted to the first 21 exons of the USH2A gene.…”

Section: Introductionmentioning

confidence: 89%

The USH2A c.2299delG mutation: dating its common origin in a Southern European population

et al. 2010

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A Mutation (2314delG) in the Usher Syndrome Type IIA Gene: High Prevalence and Phenotypic Variation

Cited by 78 publications

References 12 publications

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

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

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

The USH2A c.2299delG mutation: dating its common origin in a Southern European population

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