Mutation analysis of the MYO7A and CDH23 genes in Japanese patients with Usher syndrome type 1

Nakanishi, Hiroshi; Ohtsubo, Masafumi; Iwasaki, Satoshi; Hotta, Yoshihiro; Takizawa, Yoshinori; Hosono, Katsuhiro; Mizuta, Kunihiro; Mineta, Hiroyuki; Minoshima, Shinsei

doi:10.1038/jhg.2010.115

Cited by 24 publications

(12 citation statements)

References 29 publications

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“…PCDH15 :c.158-1G>A, predicted to alter the splice donor site of intron 3, has been classified as pathogenic. MYO7A :p.Ala771Ser is a non-truncating mutation, but was previously reported as disease-causing [13]. So, we consider the patient to be the first reported case of MYO7A / PCDH15 digenic inheritance.…”

Section: Discussionmentioning

confidence: 84%

“…In Caucasian USH1 patients, previous studies showed that mutations in MYO7A , USH1C , CDH23 , PCDH15 , and USH1G , were found in 39–55%, 7–14%, 7–35%, 7–11%, and 0–7%, respectively (the frequency of CIB2 is still unknown) [10], [11], [12]. In Japanese, Nakanishi et al showed that MYO7A and CDH23 mutations are present in USH1 patients [13], however, the frequency is not yet known. In addition, mutations in three corresponding genes (usherin USH2A [14], G protein-coupled receptor 98; GPR98 [15], and deafness, autosomal recessive 31; DFNB31 [16]) have been reported so far in USH2, and USH3 is caused by mutations in the clarin 1 ( CLRN1 ) [17] gene.…”

Section: Introductionmentioning

confidence: 99%

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Massively Parallel DNA Sequencing Facilitates Diagnosis of Patients with Usher Syndrome Type 1

et al. 2014

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Usher syndrome is an autosomal recessive disorder manifesting hearing loss, retinitis pigmentosa and vestibular dysfunction, and having three clinical subtypes. Usher syndrome type 1 is the most severe subtype due to its profound hearing loss, lack of vestibular responses, and retinitis pigmentosa that appears in prepuberty. Six of the corresponding genes have been identified, making early diagnosis through DNA testing possible, with many immediate and several long-term advantages for patients and their families. However, the conventional genetic techniques, such as direct sequence analysis, are both time-consuming and expensive. Targeted exon sequencing of selected genes using the massively parallel DNA sequencing technology will potentially enable us to systematically tackle previously intractable monogenic disorders and improve molecular diagnosis.Using this technique combined with direct sequence analysis, we screened 17 unrelated Usher syndrome type 1 patients and detected probable pathogenic variants in the 16 of them (94.1%) who carried at least one mutation. Seven patients had the MYO7A mutation (41.2%), which is the most common type in Japanese. Most of the mutations were detected by only the massively parallel DNA sequencing. We report here four patients, who had probable pathogenic mutations in two different Usher syndrome type 1 genes, and one case of MYO7A/PCDH15 digenic inheritance.This is the first report of Usher syndrome mutation analysis using massively parallel DNA sequencing and the frequency of Usher syndrome type 1 genes in Japanese. Mutation screening using this technique has the power to quickly identify mutations of many causative genes while maintaining cost-benefit performance. In addition, the simultaneous mutation analysis of large numbers of genes is useful for detecting mutations in different genes that are possibly disease modifiers or of digenic inheritance.

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Section: Discussionmentioning

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Massively Parallel DNA Sequencing Facilitates Diagnosis of Patients with Usher Syndrome Type 1

et al. 2014

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“…MYO7A is the major gene responsible for USH1 and mutations in MYO7A alone account for 70% of USH1. CDH23 is the second commonly mutated gene and mutations in MYO7A and CDH23 together account for 80% of USH1 [11], [12]. Mutations in three genes, USH2A [ 13 ], GPR98 [ 14 ], and DFNB31/WHRN [ 15 ] have been identified as disease-causing for USH2.…”

Section: Introductionmentioning

confidence: 99%

Molecular Genetics of the Usher Syndrome in Lebanon: Identification of 11 Novel Protein Truncating Mutations by Whole Exome Sequencing

Reddy

Fahiminiya

Zir³

et al. 2014

PLoS ONE

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BackgroundUsher syndrome (USH) is a genetically heterogeneous condition with ten disease-causing genes. The spectrum of genes and mutations causing USH in the Lebanese and Middle Eastern populations has not been described. Consequently, diagnostic approaches designed to screen for previously reported mutations were unlikely to identify the mutations in 11 unrelated families, eight of Lebanese and three of Middle Eastern origins. In addition, six of the ten USH genes consist of more than 20 exons, each, which made mutational analysis by Sanger sequencing of PCR-amplified exons from genomic DNA tedious and costly. The study was aimed at the identification of USH causing genes and mutations in 11 unrelated families with USH type I or II.MethodsWhole exome sequencing followed by expanded familial validation by Sanger sequencing.ResultsWe identified disease-causing mutations in all the analyzed patients in four USH genes, MYO7A, USH2A, GPR98 and CDH23. Eleven of the mutations were novel and protein truncating, including a complex rearrangement in GPR98.ConclusionOur data highlight the genetic diversity of Usher syndrome in the Lebanese population and the time and cost-effectiveness of whole exome sequencing approach for mutation analysis of genetically heterogeneous conditions caused by large genes.

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“…Mutations in these genes affect the pressure-sensitive stereocilia of the inner ear (Hereditary Hearing Loss Homepage, http://hereditaryhearingloss.org/) and do not occur at the same frequencies across ethnicities. Of all pathogenic mutations, 29∼55% are in the MYO7A gene [4], [5], [6], [7], [8], [9], [10], [11].…”

Section: Introductionmentioning

confidence: 99%

Novel Compound Heterozygous Mutations in MYO7A Associated with Usher Syndrome 1 in a Chinese Family

et al. 2014

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Usher syndrome is an autosomal recessive disease characterized by sensorineural hearing loss, age-dependent retinitis pigmentosa (RP), and occasionally vestibular dysfunction. The most severe form is Usher syndrome type 1 (USH1). Mutations in the MYO7A gene are responsible for USH1 and account for 29–55% of USH1 cases. Here, we characterized a Chinese family (no. 7162) with USH1. Combining the targeted capture of 131 known deafness genes, next-generation sequencing, and bioinformatic analysis, we identified two deleterious compound heterozygous mutations in the MYO7A gene: a reported missense mutation c.73G>A (p.G25R) and a novel nonsense mutation c.462C>A (p.C154X). The two compound variants are absent in 219 ethnicity-matched controls, co-segregates with the USH clinical phenotypes, including hearing loss, vestibular dysfunction, and age-dependent penetrance of progressive RP, in family 7162. Therefore, we concluded that the USH1 in this family was caused by compound heterozygous mutations in MYO7A.

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Mutation analysis of the MYO7A and CDH23 genes in Japanese patients with Usher syndrome type 1

Cited by 24 publications

References 29 publications

Massively Parallel DNA Sequencing Facilitates Diagnosis of Patients with Usher Syndrome Type 1

Massively Parallel DNA Sequencing Facilitates Diagnosis of Patients with Usher Syndrome Type 1

Molecular Genetics of the Usher Syndrome in Lebanon: Identification of 11 Novel Protein Truncating Mutations by Whole Exome Sequencing

Novel Compound Heterozygous Mutations in MYO7A Associated with Usher Syndrome 1 in a Chinese Family

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