Molecular Investigation of Pediatric Portuguese Patients with Sensorineural Hearing Loss

The understanding of the molecular genetics in sensorineural hearing loss (SNHL) has advanced rapidly during the last decade, but the molecular etiology of hearing impairment in the Portuguese population has not been investigated thoroughly. To provide appropriate genetic testing and counseling to families, we analyzed the whole mitochondrial genome in 95 unrelated children with SNHL (53 nonsyndromic and 42 syndromic) and searched for variations in two frequent genes, GJB2 and GJB6, in the non-syndromic patients. Mutations in mtDNA were detected in 4.2% of the cases, including a hitherto undescribed change in the mtDNA-tRNATrp gene (namely, m.5558A>G). We also identified mono- or biallelic GJB2 mutations in 20 of 53 non-syndromic cases and also detected two novel mutations (p.P70R and p.R127QfsX84). Our data further reinforce the notion that genetic heterogeneity is paramount in children with SNHL.

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Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss

Human Molecular Genetics ◽

10.1093/hmg/ddn114 ◽

2008 ◽

Vol 17 (14) ◽

pp. 2150-2159 ◽

Cited By ~ 67

Author(s):

A. Rajab ◽

D. Kelberman ◽

S. C.P. de Castro ◽

H. Biebermann ◽

H. Shaikh ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Sensorineural Hearing ◽

Novel Mutations

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Audit of the Aetiological Investigations Performed in Children with Sensorineural Hearing Loss At Salford

Manchester Medical Journal ◽

10.7227/mmj.0031 ◽

2021 ◽

Vol 3 (1) ◽

Author(s):

Saud K AlHajeri ◽

Dr Mohammed Iqbal

Keyword(s):

Hearing Loss ◽

Genetic Testing ◽

Sensorineural Hearing Loss ◽

Genetic Counselling ◽

Gold Standard ◽

Sensorineural Hearing ◽

British Association ◽

Hearing Tests ◽

Work Up

Objective: This project aims to look at the Audiovestibular Physician’s practice at Salford and how closely it aligns with the gold standard guidelines set in the protocol lately published by the British Association of Audiological Physicians. Method: An audit was done retrospectively on 20 patients suffering from sensorineural hearing loss. As such, patient notes were utilised to ascertain which aetiological investigations have been completed and which were not. Any inadequacy in the aetiological work up has been dissected to help know the underlying reasons. Results: All patients had a thorough history taken and were comprehensively physically examined. 95% of patients underwent imaging in the form of MRI/CT. 80% received CMV testing. 75% underwent ECG testing. 60% received family hearing tests. Only 35% had ophthalmology examinations and 25% underwent urine and genetic testing. Conclusion: In some cases, the low compliance rates were due to the Audiovestibular Physician not ordering the investigation as part of the aetiological work up. This could be improved with the use of a dedicated checklist to act as an aid to the physician. Moreover, genetic counselling has been proposed to attempt to boost the compliance rates with genetic testing and similarly, leaflets briefing patients’ families about the importance of undergoing hearing tests themselves is another promising proposition to help improve the adherence

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Novel Mutations in LRTOMT Associated with Congenital Profound Sensorineural Hearing Loss in a Chinese Patient

Russian Journal of Genetics ◽

10.1134/s1022795421110144 ◽

2021 ◽

Vol 57 (11) ◽

pp. 1322-1327

Author(s):

Y. Wang ◽

Y. Ma ◽

Y. Qin ◽

Zh. Zeng ◽

Zh. Zhong ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Chinese Patient ◽

Sensorineural Hearing ◽

Novel Mutations

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Novel mutations in the KCNJ10 gene associated to a distinctive ataxia, sensorineural hearing loss and spasticity clinical phenotype

Neurogenetics ◽

10.1007/s10048-020-00605-6 ◽

2020 ◽

Vol 21 (2) ◽

pp. 135-143 ◽

Cited By ~ 1

Author(s):

Matias Morin ◽

Anna-Lena Forst ◽

Paula Pérez-Torre ◽

Adriano Jiménez-Escrig ◽

Verónica Barca-Tierno ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Clinical Phenotype ◽

Sensorineural Hearing ◽

Novel Mutations

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Efficacy of Connexin testing in detecting Non-syndromic Sensorineural Hearing Loss in an Indian cohort

10.1101/2020.07.30.20165530 ◽

2020 ◽

Author(s):

Jagannath Kurva ◽

Nalini Bhat ◽

Suresh K Shettigar ◽

Harshada Tawade ◽

Shagufta Shaikh ◽

...

Keyword(s):

Hearing Loss ◽

Genetic Testing ◽

Sensorineural Hearing Loss ◽

Indian Population ◽

Sensorineural Hearing ◽

Gjb2 Gene ◽

Compound Heterozygous ◽

Missense Mutations ◽

Pathogenic Mutations ◽

Chinese Studies

Hearing loss is one of the most common sensory disorder and approximately 466 million people have disabling hearing loss worldwide. This study was conducted to identify the mutations in the GJB2, GJB3, and GJB6 genes in an Indian cohort with non-syndromic sensorineural hearing loss and ascertain its use for genetic testing. 31 affected individuals with prelingual bilateral non-syndromic severe to profound sensorineural hearing loss were identified based on clinical evaluation and audiometric assessment. Sanger Sequencing method was used. Six out of 31 affected individuals showed pathogenic nonsense mutations in GJB2 gene, accounting to 19.3%. Of the 6 affected individuals, 5 were homozygous for c.71G>A(p.Trp24Ter) and one was compound heterozygous for c.71G>A and c.370C>T(p.Gln124Ter). Missense mutations [c.380G>A(p.Arg127His) and c.457G>A(p.Val153Ile)], and 3' UTR variations were also identified in GJB2 gene. GJB3 and GJB6 genes showed only silent mutations and 3' UTR variations. 19.3% of affected individuals showing pathogenic mutations in GJB2 gene in our cohort is comparable to other Indian studies (approximately 20%) and it is less as compared to Caucasian, Japanese, and Chinese studies (approximately 50%). Lower occurrence of pathogenic mutations in GJB2 gene in our cohort and other Indian studies as compared to other Caucasian, Japanese and Chinese studies, and absence of pathogenic mutations in GJB3 and GJB6 genes indicates that these genes may have a limited role in the Indian population. Hence there is a need to identify genes that play a major role in the Indian population so that they can be used for genetic testing for NHSL to aid in accurate and early diagnosis.

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Novel mutations in ATP6V0A4 are associated with atypical progressive sensorineural hearing loss in a Chinese patient with distal renal tubular acidosis

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2011.10.017 ◽

2012 ◽

Vol 76 (1) ◽

pp. 152-154 ◽

Cited By ~ 5

Author(s):

Xiaohua Li ◽

Yongchuan Chai ◽

Zheng Tao ◽

Lei Li ◽

Zhiwu Huang ◽

...

Keyword(s):

Hearing Loss ◽

Sensorineural Hearing Loss ◽

Renal Tubular Acidosis ◽

Chinese Patient ◽

Distal Renal Tubular Acidosis ◽

Sensorineural Hearing ◽

Novel Mutations ◽

Renal Tubular

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Genetic background in late-onset sensorineural hearing loss patients

Journal of Human Genetics ◽

10.1038/s10038-021-00990-2 ◽

2021 ◽

Author(s):

Natsumi Uehara ◽

Takeshi Fujita ◽

Daisuke Yamashita ◽

Jun Yokoi ◽

Sayaka Katsunuma ◽

...

Keyword(s):

Hearing Loss ◽

Genetic Testing ◽

Sensorineural Hearing Loss ◽

Late Onset ◽

Japanese Patients ◽

Sensorineural Hearing ◽

The Other ◽

Mild Phenotype ◽

Appropriate Treatment ◽

Bilateral Sensorineural Hearing Loss

AbstractGenetic testing for congenital or early-onset hearing loss patients has become a common diagnostic option in many countries. On the other hand, there are few late-onset hearing loss patients receiving genetic testing, as late-onset hearing loss is believed to be a complex disorder and the diagnostic rate for genetic testing in late-onset patients is lower than that for the congenital cases. To date, the etiology of late-onset hearing loss is largely unknown. In the present study, we recruited 48 unrelated Japanese patients with late-onset bilateral sensorineural hearing loss, and performed genetic analysis of 63 known deafness gene using massively parallel DNA sequencing. As a result, we identified 25 possibly causative variants in 29 patients (60.4%). The present results clearly indicated that various genes are involved in late-onset hearing loss and a significant portion of cases of late-onset hearing loss is due to genetic causes. In addition, we identified two interesting cases for whom we could expand the phenotypic description. One case with a novel MYO7A variant showed a milder phenotype with progressive hearing loss and late-onset retinitis pigmentosa. The other case presented with Stickler syndrome with a mild phenotype caused by a homozygous frameshift COL9A3 variant. In conclusion, comprehensive genetic testing for late-onset hearing loss patients is necessary to obtain accurate diagnosis and to provide more appropriate treatment for these patients.

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Racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing for sensorineural hearing loss

Human Genetics ◽

10.1007/s00439-021-02338-4 ◽

2021 ◽

Author(s):

Michelle M. Florentine ◽

Stephanie L. Rouse ◽

Jihyun Stephans ◽

David Conrad ◽

Josephine Czechowicz ◽

...

Keyword(s):

Hearing Loss ◽

Genetic Testing ◽

Sensorineural Hearing Loss ◽

Genetic Diagnosis ◽

Ethnic Disparities ◽

Black Children ◽

Sensorineural Hearing ◽

Unknown Etiology ◽

Racial And Ethnic Disparities ◽

Diagnostic Efficacy

AbstractUnderstanding racial and ethnic disparities in diagnostic rates of genetic testing is critical for health equity. We sought to understand the extent and cause of racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing (CGT) for sensorineural hearing loss (SNHL). We performed a retrospective cohort study at two tertiary children’s hospitals on a diverse cohort of 240 consecutive pediatric patients (76% publicly insured, 82% non-White) with SNHL of unknown etiology who underwent CGT. Definite and possible genetic diagnoses were assigned for each patient, representing the likelihood of a genetic cause of hearing loss. Associations between diagnostic rates were examined. 3.8 ± 2.1 variants were detected per patient; this frequency did not vary between White/Asian and Hispanic/Black cohorts. Overall, 82% of variants were variants of uncertain significance (VUS). Compared with White and Asian subjects, variants identified among Hispanic and Black children were less likely to be classified as pathogenic/likely pathogenic (15% vs. 24%, p < 0.001), and Hispanic and Black children were less likely to have a definite genetic diagnosis (10% vs. 37%, p < 0.001). The adjusted odds ratio for definite genetic diagnosis in Black and Hispanic children compared with White and Asian children was 0.19. Expanding genetic diagnostic criteria to include predicted deleterious VUSs reduced these disparities between White/Asian and Hispanic/Black children, with comparable molecular diagnostic rates (41% vs. 38%, p = 0.72). However, in silico predictions are insufficiently valid for clinical use. Increased inclusion of underrepresented groups in genetic hearing-loss studies to clinically validate these variants is necessary to reduce racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing.

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