Development of a genotyping microarray for Usher syndrome

Cremers, Frans P.M.; Kimberling, William J.; Külm, Maigi; Brouwer, Arjan Pm de; Wijk, Erwin van; Brinke, Heleen te; Cremers, C.W.R.J.; Hoefsloot, Lies H.; Banfi, Sandro; Simonelli, Francesca; Fleischhauer, Johannes; Berger, Wolfgang; Kelley, Phil M.; Haralambous, Elene; Bitner‐Glindzicz, Maria; Webster, Andrew R.; Saihan, Zubin; Baere, Elfride De; Leroy, Bart P.; Silvestri, Guido; McKay, Gareth J.; Koenekoop, Robert K.; Millán, José María; Rosenberg, Thomas; Joensuu, Tarja; Sankila, Eeva Marja; Weil, Dominique; Weston, Michael D.; Wissinger, Bernd; Kremer, Hannie

doi:10.1136/jmg.2006.044784

Cited by 88 publications

(76 citation statements)

References 69 publications

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“…Exceptions were c.187C>T (p.R63X), c.1876C>T (p.R626X) and c.11864C>T (p.W3955X) that were found on 4, 4 and 7 chromosomes, respectively. In agreement with Cremers et al (2007) who recently described p.W3955X to be common among European and American USH2 patients, p.W3955X was the only nonsense mutation detected in patients from all three Scandinavian countries. Nonsense mutation c.2983C>T (p.Q933X) was detected in two Danish families, however curiously, in one of the families the 933X allele coexisted in cis with another nonsense mutation, c.2023C>T (p.Q675X).…”

Section: Usherin Truncating Mutationssupporting

confidence: 65%

“…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%

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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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Section: Usherin Truncating Mutationssupporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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“…Gene mutation testing in syndromic RP was performed by first analysing 430 known variants in eight Usher syndromeassociated genes (CDH23, MYO7A, PCDH15, Harmonin, SANS, Usherin, VLGR1, and USH3A) by the Apex array technology. 30 These genes carry mutations in patients with various types of Usher syndrome including USH1b, USH1c, USH1d, USH1f, USH1g, USH2a, USH2c, and USH3a. Positive findings with the array hybridizations were subsequently verified by DNA sequencing.…”

Section: Methodsmentioning

confidence: 99%

Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa

Kellner

Weber

et al. 2008

Eye

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Aims To compare melanin-related nearinfrared fundus autofluorescence (FAF; NIA, excitation 787 nm, emission 4800 nm) with lipofuscin-related FAF (excitation 488 nm, emission 4500 nm) in retinitis pigmentosa (RP). Methods Thirty-three consecutive RP patients with different modes of inheritance were diagnosed clinically, with full-field ERG, and if possible with molecular genetic methods. FAF and NIA imaging were performed with a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2). Results Rings of increased FAF were present within an area of preserved retinal pigment epithelium (RPE) at the posterior pole (31/33). Rings of increased NIA were located in the same region as rings of increased FAF. In contrast to FAF, NIA showed a precipitous decline of NIA peripheral to the ring. In larger areas of preserved NIA (11/31), pericentral and foveal NIA were of similar intensity with an area of lower NIA in between. In smaller areas of preserved NIA (20/31), NIA was homogeneous from the perifovea to the fovea. In one patient without a ring of increased FAF, NIA distribution was normal. In the remaining patient with severely advanced RP, no residual RPE as well as no FAF and NIA were detectable. Conclusion Characteristic features for FAF and NIA alterations in a heterogeneous group of RP patients indicate a common pathway of RPE degeneration. Patterns of NIA and FAF indicate different pathophysiologic processes involving melanin and lipofuscin. Combined NIA and FAF imaging will provide further insight into the pathogenesis of RP and noninvasive monitoring of future therapeutic interventions.

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“…For HL, several studies using microarrays have proposed high-throughput techniques for screening mutations in deafness genes and have demonstrated accurate and reliable results (19,22,23). As some mutations on the mutation panels have only been identified in Caucasians or in other specific populations, genetic screening based on the mutation spectrum of a specific population may be an appropriate and effective strategy for detecting mutations in causative genes.…”

Section: Discussionmentioning

confidence: 99%

Application of allele-specific primer extension-based microarray for simultaneous multi-gene mutation screening in patients with non-syndromic hearing loss

Choi

Lee²,

Kim³

et al. 2010

Int J Mol Med

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Abstract. Congenital hearing loss (HL) is the most common sensory disorder in humans, affecting one in 1000 infants at birth. A high degree of genetic heterogeneity makes it difficult to screen for mutations in all known deafness genes in clinical applications. We have improved a genotyping microarray using the multiplex PCR-based allele-specific primer extension (ASPE) reaction and applied this method for the genetic diagnosis of congenital HL in Korea. Seven different mutations in the GJB2, SLC26A4 and mitochondrial 12S rRNA genes, which were identified on the basis of a previous study in a Korean population, were selected for the study. These genes were used to evaluate the accuracy of the microarray. The test for validation of the current version of HL genotyping micro-array was fully concordant with the results of DNA sequencing in which 51 subjects with non-syndromic HL were originally genotyped. Furthermore, the blind test of the genotyping microarray detected four different mutations in 10 out of 65 patients, and the accuracy of microarray was calculated as 98% (64/65). Therefore, our results suggest that this HL genotyping microarray will be useful in clinical applications for the genetic diagnosis of HL.

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Development of a genotyping microarray for Usher syndrome

Cited by 88 publications

References 69 publications

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

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

Lipofuscin- and melanin-related fundus autofluorescence visualize different retinal pigment epithelial alterations in patients with retinitis pigmentosa

Application of allele-specific primer extension-based microarray for simultaneous multi-gene mutation screening in patients with non-syndromic hearing loss

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