Novel Mutations in GRXCR1 at DFNB25 Lead to Progressive Hearing Loss and Dizziness

Objective: We identified 2 patients in 1 family who had novel mutations in GRXCR1, which caused progressive hearing loss. Methods: One thousand one hundred twenty Japanese hearing loss patients with sensorineural hearing loss from unrelated families were enrolled in this study. Targeted genomic enrichment with massively parallel sequencing of all known nonsyndromic hearing loss genes was used to identify the genetic causes of hearing loss. Results: In this study, 2 affected individuals with compound heterozygous mutations—c.439C>T (p.R147C) and c.784C>T (p.R262X)—in GRXCR1 were identified. The proband had moderate to severe hearing loss and suffered from dizziness with bilateral canal paralysis. Conclusion: Our cases are the first identified in the Japanese population and are consistent with previously reported cases. The frequency of mutations in GRXCR1 seems to be extremely rare. This study underscores the importance of using comprehensive genetic testing for hearing loss. Furthermore, longitudinal audiologic assessment and precise vestibular testing are necessary for a better understanding of the mechanisms of hearing loss and vestibular dysfunction caused by GRXCR1 mutations.

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Mutations in LOXHD1 Gene Cause Various Types and Severities of Hearing Loss

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489415574067 ◽

2015 ◽

Vol 124 (1_suppl) ◽

pp. 135S-141S ◽

Cited By ~ 15

Author(s):

Kentaro Mori ◽

Hideaki Moteki ◽

Yumiko Kobayashi ◽

Hela Azaiez ◽

Kevin T. Booth ◽

...

Keyword(s):

Hearing Loss ◽

Massively Parallel Sequencing ◽

Genetic Modifier ◽

Massively Parallel ◽

Compound Heterozygous ◽

Homozygous Mutation ◽

Congenital Hearing Loss ◽

Phenotype Correlation ◽

Novel Mutations ◽

Targeted Genomic Enrichment

Objective: We present 2 families that were identified with novel mutations in LOXHD1 as a cause of nonprogressive hearing loss. Methods: One thousand three hundred fourteen (1314) Japanese subjects with sensorineural hearing loss from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results: Two patients in 1 family affected with homozygous mutation c.879+1G>A in LOXHD1 showed profound congenital hearing loss, whereas 2 patients in another family with compound heterozygous mutations, c.5869G>T (p.E1957X) and c.4480C>T (p.R1494X), showed moderate to severe hearing loss. Conclusion: Mutations in LOXHD1 are extremely rare, and these cases are the first identified in a Japanese population. The genotype-phenotype correlation in LOXHD1 is still unclear. The differences in phenotypes in each patient might be the result of the nature of the mutations or the location on the gene, or be influenced by a genetic modifier.

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Hearing Loss Caused by a P2RX2 Mutation Identified in a MELAS Family With a Coexisting Mitochondrial 3243AG Mutation

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489415575045 ◽

2015 ◽

Vol 124 (1_suppl) ◽

pp. 177S-183S ◽

Cited By ~ 12

Author(s):

Hideaki Moteki ◽

Hela Azaiez ◽

Kevin T. Booth ◽

Mitsuru Hattori ◽

Ai Sato ◽

...

Keyword(s):

Hearing Loss ◽

Mitochondrial Myopathy ◽

Massively Parallel Sequencing ◽

Novel Mutation ◽

Massively Parallel ◽

Nonsyndromic Hearing Loss ◽

Potential Explanation ◽

Atp Production ◽

First Case ◽

Targeted Genomic Enrichment

Objectives: We present a family with a mitochondrial DNA 3243A>G mutation resulting in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), of which some members have hearing loss in which a novel mutation in the P2RX2 gene was identified. Methods: One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic causes of hearing loss. Results: A novel mutation in the P2RX2 gene that corresponded to c.601G>A (p.Asp201Tyr) was identified. Two patients carried the mutation and had severe sensorineural hearing loss, while other members with MELAS (who did not carry the P2RX2 mutation) had normal hearing. Conclusion: This is the first case report of a diagnosis of hearing loss caused by P2RX2 mutation in patients with MELAS. A potential explanation is that a decrease in adenosine triphosphate (ATP) production due to MELAS with a mitochondrial 3243A>G mutation might suppress activation of P2X2 receptors. We also suggest that hearing loss caused by the P2RX2 mutation might be influenced by the decrease in ATP production due to MELAS.

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Genetic testing for sporadic hearing loss using targeted massively parallel sequencing identifies 10 novel mutations

Clinical Genetics ◽

10.1111/cge.12431 ◽

2014 ◽

Vol 87 (6) ◽

pp. 588-593 ◽

Cited By ~ 34

Author(s):

X. Gu ◽

L. Guo ◽

H. Ji ◽

S. Sun ◽

R. Chai ◽

...

Keyword(s):

Hearing Loss ◽

Genetic Testing ◽

Massively Parallel Sequencing ◽

Massively Parallel ◽

Novel Mutations ◽

Parallel Sequencing

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A novel compound heterozygous mutation in the MYO15A gene in autosomal recessive hearing loss identified by targeted massively parallel sequencing

Otorhinolaryngology-Head and Neck Surgery ◽

10.15761/ohns.1000207 ◽

2019 ◽

Vol 4 (3) ◽

Author(s):

Guangjie Zhu ◽

dengbin Ma ◽

Lusen Shi ◽

Han Zhou ◽

Jie Chen ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Massively Parallel Sequencing ◽

Massively Parallel ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Parallel Sequencing

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Brief Report of Variants Detected in Hereditary Hearing Loss Cases in Iran over a 3-Year Period

Iranian Journal of Public Health ◽

10.18502/ijph.v48i10.3500 ◽

2020 ◽

Author(s):

Niloofar BAZAZZADEGAN ◽

Raheleh VAZEHAN ◽

Mahsa FADAEE ◽

Zohreh FATTAHI ◽

Ayda ABOLHASSANI ◽

...

Keyword(s):

Hearing Loss ◽

Genetic Testing ◽

Massively Parallel Sequencing ◽

Cost Effective ◽

Massively Parallel ◽

Parallel Sequencing ◽

Hereditary Hearing Loss ◽

Targeted Genomic Enrichment ◽

Novel Variants ◽

Autosomal Recessive Pattern

Background: Diagnosis of hereditary hearing loss (HHL) as a heterogeneous disorder is very important especially in countries with high rates of consanguinity where the autosomal recessive pattern of inheritance is prevalent. Techniques such as next-generation sequencing, a comprehensive genetic test using targeted genomic enrichment and massively parallel sequencing (TGE + MPS), have made the diagnosis more cost-effective. The aim of this study was to determine HHL variants with comprehensive genetic testing in our country. of this study was to determine HHL variants with comprehensive genetic testing in our country. Methods: Fifty GJB2 negative individuals with HHL were referred to the Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, one of the reference diagnostic genetic laboratories in Iran, during a 3-year period between 2014 and 2017. They were screened with the OtoSCOPE test, the targeted genomic enrichment and massively parallel sequencing (TGE + MPS) platform after a detailed history had been taken along with clinical evaluation. Results: Among 32 out of 50 GJB2 negative patients (64%), 34 known pathogenic and novel variants were detected of which 16 (47%) were novel, identified in 10 genes of which the most prevalent were CDH23, MYO7A and MYO15A. Conclusion: These results provide a foundation from which to make appropriate recommendations for the use of comprehensive genetic testing in the evaluation of Iranian patients with hereditary hearing loss.

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USH2 Caused by GPR98 Mutation Diagnosed by Massively Parallel Sequencing in Advance of the Occurrence of Visual Symptoms

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489415574070 ◽

2015 ◽

Vol 124 (1_suppl) ◽

pp. 123S-128S ◽

Cited By ~ 5

Author(s):

Hideaki Moteki ◽

Hidekane Yoshimura ◽

Hela Azaiez ◽

Kevin T. Booth ◽

A. Eliot Shearer ◽

...

Keyword(s):

Hearing Loss ◽

Massively Parallel Sequencing ◽

Usher Syndrome ◽

Genetic Diagnosis ◽

Massively Parallel ◽

Parallel Sequencing ◽

Visual Symptoms ◽

Targeted Genomic Enrichment ◽

Usher Syndrome Type

Objective: We present 2 patients who were identified with mutations in the GPR98 gene that causes Usher syndrome type 2 (USH2). Methods: One hundred ninety-four (194) Japanese subjects from unrelated families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were used to identify the genetic causes of hearing loss. Results: We identified causative mutations in the GPR98 gene in 1 family (2 siblings). The patients had moderate sloping hearing loss, and no progression was observed over a period of 10 years. Fundus examinations were normal. However, electroretinograms revealed impaired responses in both patients. Conclusion: Early diagnosis of Usher syndrome has many advantages for patients and their families. This study supports the use of comprehensive genetic diagnosis for Usher syndrome, especially prior to the onset of visual symptoms, to provide the highest chance of diagnostic success in early life stages.

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Massively Parallel Sequencing for Genetic Diagnosis of Hearing Loss

Otolaryngology ◽

10.1177/0194599815591156 ◽

2015 ◽

Vol 153 (2) ◽

pp. 175-182 ◽

Cited By ~ 68

Author(s):

A. Eliot Shearer ◽

Richard J. H. Smith

Keyword(s):

Hearing Loss ◽

Massively Parallel Sequencing ◽

Genetic Diagnosis ◽

Massively Parallel ◽

Parallel Sequencing

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Novel Mutations in LRTOMT Associated With Moderate Progressive Hearing Loss in Autosomal Recessive Inheritance

Annals of Otology Rhinology & Laryngology ◽

10.1177/0003489415575043 ◽

2015 ◽

Vol 124 (1_suppl) ◽

pp. 142S-147S ◽

Cited By ~ 4

Author(s):

Aya Ichinose ◽

Hideaki Moteki ◽

Mitsuru Hattori ◽

Shin-ya Nishio ◽

Shin-ichi Usami

Keyword(s):

Hearing Loss ◽

Massively Parallel Sequencing ◽

Autosomal Recessive Inheritance ◽

Japanese Patients ◽

Compound Heterozygous Mutation ◽

Heterozygous Mutation ◽

Compound Heterozygous ◽

Coding Region ◽

Novel Mutations ◽

First Case

Objective: We present a patient who was identified with novel mutations in the LRTOMT gene and describe the clinical features of the phenotype including serial audiological findings. Methods: One hundred six Japanese patients with mild to moderate sensorineural hearing loss from unrelated and nonconsanguineous families were enrolled in the study. Targeted genomic enrichment and massively parallel sequencing of all known nonsyndromic hearing loss genes were performed to identify the genetic cause of hearing loss. Results: Compound heterozygotes with a novel frame-shift mutation and a missense mutation were identified in the LRTOMT gene. The mutated residues were segregated in both alleles of LRTOMT, present within the LRTOMT2 protein coding region. The patient had moderate sloping hearing loss at high frequencies, which progressed at 1000 Hz and higher frequencies over a period of 6 years. Conclusion: Hearing loss caused by mutations in the LRTOMT gene is extremely rare. This is the first case report of a compound heterozygous mutation in a nonconsanguineous family.

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