Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells

Seco, Celia Zazo; Giese, Arnaud P. J.; Shafique, Sobia; Schraders, Margit; Oonk, Anne M.M.; Grossheim, Mike; Oostrik, Jaap; Strom, Tim M.; Hegde, Rashmi S.; Wijk, Erwin van; Frolenkov, Gregory I.; Azam, Maleeha; Yntema, Helger G.; Free, Rolien; Riazuddin, Saima; Verheij, Joanne; Admiraal, R.J.C.; Qamar, Raheel; Ahmed, Zubair M.; Kremer, Hannie

doi:10.1038/ejhg.2015.157

Cited by 32 publications

(46 citation statements)

References 39 publications

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“…In humans, a truncating mutation in the CLIC5 was found to be the cause of autosomal recessive deafness-103 in two siblings of Turkish decent (Seco et al, 2016). By genomic sequence analysis, tmc1 gene was mapped to the Chromosome 9q13-q21 (Kurima et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish

Yao

Wang

Mittal

et al. 2019

The Anatomical Record

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Analysis of gene expression has the potential to assist in the understanding of multiple cellular processes including proliferation, cell‐fate specification, senesence, and activity in both healthy and disease states. Zebrafish model has been increasingly used to understand the process of hearing and the development of the vertebrate auditory system. Within the zebrafish inner ear, there are three otolith organs, each containing a sensory macula of hair cells. The saccular macula is primarily involved in hearing, the utricular macula is primarily involved in balance and the function of the lagenar macula is not completely understood. The goal of this study is to understand the transcriptional differences in the sensory macula associated with different otolith organs with the intention of understanding the genetic mechanisms responsible for the distinct role each organ plays in sensory perception. The sensory maculae of the saccule, utricle, and lagena were dissected out of adult Et(krt4:GFP)sqet4 zebrafish expressing green fluorescent protein in hair cells for transcriptional analysis. The total RNAs of the maculae were isolated and analyzed by RNA GeneChip microarray. Several of the differentially expressed genes are known to be involved in deafness, otolith development and balance. Gene expression among these otolith organs was very well conserved with less than 10% of genes showing differential expression. Data from this study will help to elucidate which genes are involved in hearing and balance. Furthermore, the findings of this study will assist in the development of the zebrafish model for human hearing and balance disorders. Anat Rec, 303:527–543, 2020. © 2019 American Association for Anatomy

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Section: Resultsmentioning

confidence: 99%

Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish

Yao

Wang

Mittal

et al. 2019

The Anatomical Record

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“…12 Thirty-six patients have been previously reported in a study on the utility of WES, 11 and one patient has been reported before in a publication on novel and recurrent CIB2 variants. 13 Prior to WES, causative variants in one or more genes involved in HI had been excluded by Sanger sequencing in 137 patients. Prescreening was performed in these patients because WES was not available at that time or because the clinician had a high clinical suspicion for mutations in a specific gene.…”

Section: Patients and Methods Patientsmentioning

confidence: 99%

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands

et al. 2016

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Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes. Two hundred index patients, mostly of Dutch origin, with presumed hereditary HI underwent WES followed by targeted analysis of an HI gene panel of 120 genes. We found causative variants underlying the HI in 67 of 200 patients (33.5%). Eight of these patients have a large homozygous deletion involving STRC, OTOA or USH2A, which could only be identified by copy number variation detection. Variants of uncertain significance were found in 10 patients (5.0%). In the remaining 123 cases, no potentially causative variants were detected (61.5%). In our patient cohort, causative variants in GJB2, USH2A, MYO15A and STRC, and in MYO6 were the leading causes for autosomal recessive and dominant HI, respectively. Segregation analysis and functional analyses of variants of uncertain significance will probably further increase the diagnostic yield of WES.

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“…13 What makes it more complicated is that mutations of USH2A may lead to RP without hearing loss, 14 and mutations of all six USH1 genes may cause non-syndrome deafness. [15][16][17][18][19][20] Such complexity poses challenges to the molecular diagnosis for USH patients.…”

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confidence: 99%

Comprehensive Molecular Screening in Chinese Usher Syndrome Patients

Sun

Ren

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. The objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations. METHODS.A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations. RESULTS.We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous mutation in 1 patient (0.8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98, MYO7A, PCDH15, USH1C, and USH2A) genes; 5 other retinal degeneration genes (CHM, CNGA1, EYS, PDE6B, and TULP1); and 1 nonsyndromic hearing loss gene (MYO15A) were identified, and 78 were novel. Mutations of MYOA7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USH1C (10%). Mutations of USH2A accounted for 67.7% of USH2 families, and mutation c.8559-2A>G was the most frequent one, accounting for 19.1% of the identified USH2A alleles. CONCLUSIONS.Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future.

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Novel and recurrent CIB2 variants, associated with nonsyndromic deafness, do not affect calcium buffering and localization in hair cells

Cited by 32 publications

References 39 publications

Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish

Transcriptomic Analyses of Inner Ear Sensory Epithelia in Zebrafish

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands

Comprehensive Molecular Screening in Chinese Usher Syndrome Patients

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