A splice-site variant (c.3289-1G&gt;T) in OTOF underlies profound hearing loss in a Pakistani kindred

Ahmed, Ashfaque; Wang, Meng; Khan, Rizwan Hasan; Shah, Abid Ali; Guo, Hui; Malik, Sajid; Xia, Kun; Hu, Zhengmao

doi:10.1186/s12920-020-00859-x

Cited by 3 publications

(1 citation statement)

References 19 publications

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“… 12 Another study conducted on a Pakistani family comprising seven subjects with autosomal recessive HL found pathogenic OTOF variant c.3289-1 G>T as a risk factor for the disease. 13 In view of these significant associations between OTOF gene and hereditary deafness, it is critical to provide evidence-based information on the prevalence of OTOF variants in Pakistan and their association with the disease. So that a national genetic database on hereditary deafness could be established and extensive genetic testing be provided.…”

Section: Introductionmentioning

confidence: 99%

Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects

Naseer,

Rasid,

Majeed

et al. 2023

Pak J Med Sci

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Objective: To find possible association of R1939W and P1987R variants of OTOF gene with severe to profound NSSHL in cochlear implant subjects. Methods: It was a case control study, conducted from June 2021 to February 2022, comprising 50 cases of severe to profound NSSHL who had received cochlear implant from ENT Department, CMH Rawalpindi and 50 age-matched healthy controls from PEMH Rawalpindi. Blood samples were collected from all the subjects, followed by DNA extraction and allele-specific polymerase chain reaction, performed at Multi-disciplinary Laboratory of Department of Biochemistry and Molecular Biology, Army Medical College Rawalpindi. Statistical analysis was done using ‘SPSS’ and ‘XLSTAT’, followed by genetic analysis using ‘SNPstat’. Results: Mean age of the cases was 5.96 ± 4.62 years (N=50), comprising 58% males and 42% females. All had bilateral and prelingual HL. Parental consanguinity was 72%, whereas 62% cases had a positive family history of deafness. Alleles of R1939W and P1987R were not associated with NSSHL, as shown by their p values of 0.56 and 0.89 respectively. For R1939W ORs were 0.71 (dominant model) and 0.80 (overdominant model), indicating negative association with NSSHL. Regarding P1987R OR was 0.96 (log-additive model). Genotypes of both variants were not in HW Equilibrium (p <0.0001), whereas their alleles showed high LD (D’=0.92). Conclusion: High percentage of parental consanguinity was observed among cochlear implant candidates. The OTOF variants R1939W and P1987R were found to have protective roles against NSSHL in study population. doi: https://doi.org/10.12669/pjms.39.5.6393 How to cite this: Naseer H, Rashid A, Majeed A, Baig ZA. Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects. Pak J Med Sci. 2023;39(5):---------. doi: https://doi.org/10.12669/pjms.39.5.6393 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section: Introductionmentioning

confidence: 99%

Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects

Naseer,

Rasid,

Majeed

et al. 2023

Pak J Med Sci

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Sef fimbria operon construction, expression, and function for direct rapid detection of Salmonella Enteritidis

Hou

Liu

et al. 2021

Appl Microbiol Biotechnol

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The natural history, clinical outcomes, and genotype–phenotype relationship of otoferlin-related hearing loss: a systematic, quantitative literature review

Ford,

Riggs,

Quigley

et al. 2023

Hum. Genet.

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Congenital hearing loss affects one in 500 newborns. Sequence variations in OTOF, which encodes the calcium-binding protein otoferlin, are responsible for 1–8% of congenital, nonsyndromic hearing loss and are the leading cause of auditory neuropathy spectrum disorders. The natural history of otoferlin-related hearing loss, the relationship between OTOF genotype and hearing loss phenotype, and the outcomes of clinical practices in patients with this genetic disorder are incompletely understood because most analyses have reported on small numbers of cases with homogeneous OTOF genotypes. Here, we present the first systematic, quantitative literature review of otoferlin-related hearing loss, which analyzes patient-specific data from 422 individuals across 61 publications. While most patients display a typical phenotype of severe-to-profound hearing loss with prelingual onset, 10–15% of patients display atypical phenotypes, including mild-to-moderate, progressive, and temperature-sensitive hearing loss. Patients’ phenotypic presentations appear to depend on their specific genotypes. For example, non-truncating variants located in and immediately downstream of the C2E calcium-binding domain are more likely to produce atypical phenotypes. Additionally, the prevalence of certain sequence variants and their associated phenotypes varies between populations due to evolutionary founder effects. Our analyses also suggest otoacoustic emissions are less common in older patients and those with two truncating OTOF variants. Critically, our review has implications for the application and limitations of clinical practices, including newborn hearing screenings, hearing aid trials, cochlear implants, and upcoming gene therapy clinical trials. We conclude by discussing the limitations of available research and recommendations for future studies on this genetic cause of hearing loss.

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A splice-site variant (c.3289-1G>T) in OTOF underlies profound hearing loss in a Pakistani kindred

Cited by 3 publications

References 19 publications

Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects

Association of R1939W and P1987R variants of Otoferlin (OTOF) gene with severe to profound nonsyndromic sensorineural hearing loss in Pakistani subjects

Sef fimbria operon construction, expression, and function for direct rapid detection of Salmonella Enteritidis

The natural history, clinical outcomes, and genotype–phenotype relationship of otoferlin-related hearing loss: a systematic, quantitative literature review

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