Mutational Spectrum and Clinical Features of Patients With <i>ACTG1</i> Mutations Identified by Massively Parallel DNA Sequencing

Miyagawa, Maiko; Nishio, Shin‐ya; Ichinose, Aya; Iwasaki, Satoshi; Murata, Takaaki; Kitajiri, Shin‐ichiro; Usami, Shin‐ichi

doi:10.1177/0003489415575057

Cited by 24 publications

(28 citation statements)

References 34 publications

(65 reference statements)

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“…The rate of progression of hearing loss caused by EYA4 was considered to be 0.63 dB/year (95%CI: 0.41-0.85 dB/year). In previous reports on ADSNHL hearing loss, the progression rate for the POU4F3 gene was 0.5-0.9 dB/year 41 , that for MYO6 was 2.0 dB/year 45 , and that for ACTG1 was 2.0-6.0 dB/ year 46 , and the results in this study suggests that the rate of hearing loss progression caused by EYA4 may be relatively mild.…”

Section: Discussionsupporting

confidence: 68%

Prevalence and clinical features of hearing loss caused by EYA4 variants

Shinagawa

Moteki

Nishio

et al. 2020

Sci Rep

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13 , takashi ishino 14 , natsumi Uehara 15 & Shin-ichi Usami 1,2* Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. We selected 1,336 autosomal dominant hearing loss patients among 7,408 unrelated Japanese hearing loss probands and performed targeted genome enrichment and massively parallel sequencing of 68 target genes for all patients. Clinical information of cases with mutations in EYA4 was gathered and analyzed from medical charts. Eleven novel EYA4 variants (three frameshift variants, three missense variants, two nonsense variants, one splicing variant, and two single-copy number losses) and two previously reported variants were found in 12 probands (0.90%) among the 1,336 autosomal dominant hearing loss families. The audiometric configuration of truncating variants tends to deteriorate for all frequencies, whereas that of non-truncating variants tends to show high-frequency hearing loss, suggesting a new correlation between genotype and phenotype in DFNA10. The rate of hearing loss progression caused by EYA4 variants was considered to be 0.63 dB/year, as found in this study and previous reports. Hearing loss is the most common sensory disorder and more than 50% of cases of congenital or early onset hearing loss are caused by genetic factors 1. Regarding hereditary hearing loss, over 100 genes are known to be causative based on genetic analysis [Hereditary Hearing Loss Homepage: https://hereditaryhearingloss.org/ accessed

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Section: Discussionsupporting

confidence: 68%

Prevalence and clinical features of hearing loss caused by EYA4 variants

Shinagawa

Moteki

Nishio

et al. 2020

Sci Rep

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“…The 11 reported mutations in 17 individuals are distributed across all four subdomains [Holmes et al, ], and include three clusters of mutations: Met153‐Ser155 (N = 4), Arg254‐Arg256 (N = 5), and Glu334‐Arg335 (N = 2). We found no overlap between mutations associated with isolated hearing loss and BWCS (HGMD and ClinVar, accessed April 2016), although two mutations affect nearby residues: p.(Lys118Met) and p.(Lys118Asn) with isolated hearing loss, and p.(Thr120Ile) with BWCS [Miyagawa et al, ; Yuan et al, ]. However, craniofacial features of DFNA20/26 patients have been neither illustrated nor discussed in detail.…”

Section: Discussionmentioning

confidence: 92%

Update on the ACTG1‐associated Baraitser–Winter cerebrofrontofacial syndrome

Donato

Kuechler

Vergano

et al. 2016

American J of Med Genetics Pt A

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Baraitser–Winter cerebrofrontofacial syndrome is caused by heterozygous missense mutations in one of the two ubiquitous cytoplasmic actin‐encoding genes ACTB and ACTG1. Recently, we characterized the large cohort of 41 patients presenting with this condition. Our series contained 34 patients with mutations in ACTB and only nine with ACTG1 mutations. Here, we report on seven unrelated patients with six mutations in ACTG1–four novel and two previously reported. Only one of seven patients was clinically diagnosed with this disorder and underwent ACTB/ACTG1 targeted sequencing, four patients were screened as a part of the large lissencephaly cohort and two were tested with exome sequencing. Retrospectively, facial features were compatible with the diagnosis but significantly milder than previously reported in four patients, and non‐specific in one. The pattern of malformations of cortical development was highly similar in four of six patients with available MRI images and encompassed frontal predominant pachygyria merging with the posterior predominant band heterotopia. Two remaining patients showed mild involvement consistent with bilaterally simplified gyration over the frontal lobes. Taken together, we expand the clinical spectrum of the ACTG1‐associated Baraitser–Winter cerebrofrontofacial syndrome demonstrating the mild end of the facial and brain manifestations. © 2016 Wiley Periodicals, Inc.

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“…Since the expression of ACTG1 is located within the cochlea, comparatively good outcomes for CI/EAS can be expected. In fact, our studies demonstrated that EAS was an effective therapeutic intervention for patients with ACTG1 mutations (Miyagawa et al, , ).…”

Section: In Patients With Specific Genetic Backgroundsmentioning

confidence: 99%

“…E : Hearing thresholds with EAS. F : Japanese monosyllable test results showing dramatic improvement with EAS (Miyagawa et al, ).…”

Section: In Patients With Specific Genetic Backgroundsmentioning

confidence: 99%

Cochlear Implantation From the Perspective of Genetic Background

Usami

Nishio

Moteki

et al. 2020

The Anatomical Record

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While cochlear implantation (CI) technology has greatly improved over the past 40 years, one aspect of CI that continues to pose difficulties is the variability of outcomes due to numerous factors involved in postimplantation performance. The electric acoustic stimulation (EAS) system has expanded indications for CI to include patients with residual hearing, and is currently becoming a standard therapy for these patients. Genetic disorders are known to be the most common cause of congenital/early‐onset sensorineural hearing loss, and are also involved in a considerable proportion of cases of late‐onset hearing loss. There has been a great deal of progress in the identification of deafness genes over the last two decades. Currently, more than 100 genes have been reported to be associated with non‐syndromic hearing loss. Patients possessing a variety of deafness gene mutations have achieved satisfactory auditory performance after CI/EAS, suggesting that identification of the genetic background facilitates prediction of post‐CI/EAS performance. When the intra‐cochlear etiology is associated with a specific genetic background, there is a potential for good CI performance. Thus, it is essential to determine which region of the cochlea is affected by identifying the responsible genes. This review summarizes the genetic background of the patients receiving CI/EAS, and introduces detailed clinical data and CI/EAS outcomes in representative examples. Anat Rec, 303:563–593, 2020. © 2020 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

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Mutational Spectrum and Clinical Features of Patients With ACTG1 Mutations Identified by Massively Parallel DNA Sequencing

Abstract: Target exon-sequencing using MPS was proven to be a powerful new clinical diagnostic tool for the identification of rare causative genes such as ACTG1. The present clinical findings not only confirmed those previous reports but also provided important new clinical information.

Cited by 24 publications

References 34 publications

Prevalence and clinical features of hearing loss caused by EYA4 variants

Prevalence and clinical features of hearing loss caused by EYA4 variants

Update on the ACTG1‐associated Baraitser–Winter cerebrofrontofacial syndrome

Cochlear Implantation From the Perspective of Genetic Background

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