Genotype-Phenotype Correlation for DFNA22: Characterization of Non-Syndromic, Autosomal Dominant, Progressive Sensorineural Hearing Loss due to MYO6 Mutations

2010 ◽  
Vol 15 (4) ◽  
pp. 211-220 ◽  
Author(s):  
Vedat Topsakal ◽  
Nele Hilgert ◽  
Joost van Dinther ◽  
Lisbeth Tranebjærg ◽  
Nanna D. Rendtorff ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Autosomal Dominant ◽  
Sensorineural Hearing ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

Novel TECTA Mutations Identified in Stable Sensorineural Hearing Loss and Their Clinical Implications

2014 ◽  
Vol 20 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Ah Reum Kim ◽  
Mun Young Chang ◽  
Ja-Won Koo ◽  
Seung Ha Oh ◽  
Byung Yoon Choi
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
High Frequency ◽  
Autosomal Dominant ◽  
Sensorineural Hearing ◽  
Clinical Feature ◽  
Phenotype Correlation ◽  
Causative Gene ◽  
Bioinformatics Analyses ◽  
Genotype Phenotype Correlation

TECTA is a causative gene of autosomal dominant (DFNA8/A12) and autosomal recessive (DFNB 21) nonsyndromic sensorineural hearing loss (NSHL). Mutations in TECTA account for 4% of all autosomal dominant NSHL cases in some populations and are thus thought to be one of the major causes of autosomal dominant NSHL. A genotype-phenotype correlation for autosomal dominant mutations in the TECTA gene has been proposed. Two families (SB146 and SB149), which segregated moderate NSHL in an autosomal dominant fashion, were included in this study. We performed targeted resequencing of 134 known deafness genes (TRS-134) and bioinformatics analyses to find causative mutations for NSHL in these 2 families. Through TRS-134, we detected 2 novel mutations, i.e. c.3995G>T (p.C1332F) and c.5618C>T (p.T1873I), in the TECTA gene. These mutations cosegregated with NSHL in the studied families and were not detected in normal controls. The mutations c.3995G>T and c.5618C>T reside in the von Willebrand factor type D3-D4 (vWFD3-D4) interdomain of the zonadhesin (ZA) domain and the zona pellucida (ZP) domain, respectively. p.C1332F is the first mutation detected in the vWFD3-D4 interdomain of the ZA domain. The mutations p.C1332F and p.T1873I were associated with stable high-frequency and mid-frequency hearing loss, respectively. Notably, the cysteine residue mutated to phenylalanine in SB146 was not related to progression of sensorineural hearing loss, which argues against the previous hypothesis. Here we confirm a known genotype-phenotype correlation for the ZP domain and propose a hypothetical genotype-phenotype correlation which relates mutations in vWFD3-D4 to stable high-frequency NSHL in Koreans. This clinical feature makes subjects with the missense mutation in the vWFD3-D4 interdomain of TECTA potentially good candidates for middle ear implantation. i 2014 S. Karger AG, Basel

Novel genotype–phenotype correlation of functionally characterized LMX1A variants linked to sensorineural hearing loss

2020 ◽  
Vol 41 (11) ◽  
pp. 1877-1883 ◽  
Author(s):  
Sang‐Yeon Lee ◽  
Jin Hee Han ◽  
Marge Carandang ◽  
Min Young Kim ◽  
Bonggi Kim ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Novel Genotype

scholarly journals Severe or Profound Sensorineural Hearing Loss Caused by Novel USH2A Variants in Korea: Potential Genotype-Phenotype Correlation

2020 ◽  
Vol 13 (2) ◽  
pp. 113-122 ◽  
Author(s):  
Sang-Yeon Lee ◽  
Kwangsic Joo ◽  
Jayoung Oh ◽  
Jin Hee Han ◽  
Hye-Rim Park ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Cochlear Implantation ◽  
Usher Syndrome ◽  
Sensorineural Hearing ◽  
Compound Heterozygous ◽  
Compound Heterozygosity ◽  
Phenotype Correlation ◽  
Truncating Mutation ◽  
Genotype Phenotype Correlation

Objectives. We, herein, report two novel <i>USH2A</i> variants from two unrelated Korean families and their clinical phenotypes, with attention to severe or more than severe sensorineural hearing loss (SNHL).Methods. Two postlingually deafened subjects (SB237-461, M/46 and SB354-692, F/34) with more than severe SNHL and also with suspicion of Usher syndrome type II (USH2) were enrolled. A comprehensive audiological and ophthalmological assessments were evaluated. We conducted the whole exome sequencing and subsequent pathogenicity prediction analysis.Results. We identified the following variants of <i>USH2A</i> from the two probands manifesting more than severe SNHL and retinitis pigmentosa (RP): compound heterozygosity for a nonsense (c.8176C>T: p.R2723X) and a missense variant (c.1823G>A: p.C608Y) in SB237, and compound heterozygosity for two frameshift variants (c.14835delT: p.S4945fs & c.13112_13115delAAAT: p.G4371fs) in SB354. Based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines, two novel variants, c.1823G>A: p.C608Y and c.14835delT: p.Ser4945fs, can be classified as “uncertain significance” and “pathogenic,” respectively. The audiogram exhibited more than severe SNHL and a down-sloping configuration, necessitating cochlear implantation. The ophthalmic examinations revealed typical features of RP. Interestingly, one proband (SB 354-692) carrying two truncating compound heterozygous variants exhibited more severe hearing loss than the other proband (SB 237-461), carrying one truncation with one missense variant.Conclusion. Our results provide insight on the expansion of audiological spectrum encompassing more than severe SNHL in Korean subjects harboring <i>USH2A</i> variants, suggesting that <i>USH2A</i> should also be included in the candidate gene of cochlear implantation. A specific combination of <i>USH2A</i> variants causing truncating proteins in both alleles could demonstrate more severe audiological phenotype than that of <i>USH2A</i> variants carrying one truncating mutation and one missense mutation, suggesting a possible genotype-phenotype correlation. The understanding of audiological complexity associated with <i>USH2A</i> will be helpful for genetic counseling and treatment starategy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) presenting with sudden sensorineural hearing loss

2005 ◽  
Vol 119 (2) ◽  
pp. 148-151 ◽  
Author(s):  
John S Phillips ◽  
Jacquelyn A King ◽  
Siddharthan Chandran ◽  
Peter R Prinsley ◽  
David Dick
Keyword(s):  
Hearing Loss ◽  
Family History ◽  
Sensorineural Hearing Loss ◽  
World Literature ◽  
Autosomal Dominant ◽  
Sudden Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Cerebrovascular Events ◽  
The World

CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is an autosomal dominant angiopathy characterized by recurrent cerebrovascular events, migraine and dementia. We describe a case of sensorineural hearing loss as the presenting feature of this condition. We have found no previous reports in the world literature of CADASIL presenting with a sudden sensorineural hearing loss. The significance of questioning a patient with regard to family history is exemplified in this case.

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