Novel deleterious mutation in MYO7A, TH and EVC2 in two Pakistani brothers with familial deafness

Sabiha, Bibi; Ali, Johar; Yousafzai, Yasar Mehmood; Haider, Syed Adnan

doi:10.12669/pjms.35.1.98

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…R1939W and P1987R variants of OTOF gene were found to be protective against NSSHL in our study subjects, suggesting other pathogenic variants of this gene or other genes 23 , 24 as probable risk factors for hereditary HL in Pakistani population. This study has added to the national database of single nucleotide polymorphisms associated with HL, that will aid in selection of variants for future genetic testing and screening of hereditary HL.…”

Section: Discussionsupporting

confidence: 50%

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: Discussionsupporting

confidence: 50%

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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“…Similar to ARHGEF40 and BRD9, the function of CDH23 has not been established hitherto [47] in spite of being implicated in Usher syndrome type ID and non-syndromic hearing loss [50]. CDH23 belongs to the cadherin family, a family that mediates calcium-dependent cell adhesion [51].…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma

Campos¹,

Fragoso²,

Luís³

et al. 2020

Genes

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Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. CDH23, ARHGEF40, and BRD9 were identified as the most promising susceptibility genes in hereditary melanoma. In silico analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of CDH23, ARHGEF40, and BRD9 expression in sporadic melanoma by using the TCGA dataset (n = 461). No differences were observed in BRD9 expression between melanoma and normal skin samples, nor with melanoma stage, whereas ARHGEF40 was found overexpressed, and CDH23 was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma.

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“…The FASTQ (raw data) file produced using the illumina Hiseq was filtered to remove low-quality reads ( Q > 30) using CASAVA and the trimometric tool [ 45 , 46 ]. The filtered reads were then aligned to the reference genome (hg19/GRCh37) using BWA-mem (v 0.7.130) [ 47 , 48 ]. Base recalibration was performed using GATAK (v 3.2.2).…”

Section: Methodsmentioning

confidence: 99%

Association between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of Khyber Pakhtunkwha, Pakistan

Shah

Jan

Khan

et al. 2023

Genes

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Genome-wide association studies significantly increased the number of hypertension risk variants; however, most of them focused on European societies. There is lack of such studies in developing countries, including Pakistan. The lack of research studies and the high prevalence of hypertension in the Pakistani community prompted us to design this study. Aldosterone synthase (CYP11B2) was thoroughly studied in different ethnic groups; however, no such study has been conducted in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. In essential hypertension, the aldosterone synthase gene (CYP11B2) plays a significant role. Aldosterone synthesis is affected by both hereditary and environmental factors. Aldosterone synthase (encoded by the CYP11B2 gene) controls the conversion of deoxycorticosterone to aldosterone and, thus, has genetic influences. Polymorphisms in the CYP11B2 gene are linked to an increased risk of hypertension. Previous research on the polymorphism of the aldosterone synthase (CYP11B2) gene and its relationship to hypertension produced inconclusive results. The present study investigates the relationship between CYP11B2 gene polymorphism and hypertension in Pakistan’s Pashtun population. We used the nascent exome sequencing method to identify variants associated with hypertension. The research was divided into two phases. In phase one, DNA samples from 200 adult hypertension patients (of age ≥ 30 years) and 200 controls were pooled (n = 200/pool) and subjected to Exome Sequencing. In the second phase, the WES reported SNPs were genotyped using the Mass ARRAY technique to verify and confirm the association between WES-identified SNPs and hypertension. WES identified a total of eight genetic variants in the CYP11B2 gene. The chi-square test and logistic regression analysis were used to estimate the minor allele frequencies (MAFs) and chosen SNPs relationships with hypertension. The frequency of minor allele T was found to be higher in cases compared to the control (42% vs. 30%: p = 0.001) for rs1799998 of CYP11B2 gene, while no significant results (p > 0.05) were observed for the remaining SNPs; rs4536, rs4537, rs4545, rs4543, rs4539, rs4546 and rs6418 showed no positive association with HTN in the studied population (all p > 0.05). Our study findings suggest that rs1799998 increases susceptibly to HTN in the Pashtun population of KP, Pakistan.

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Novel deleterious mutation in MYO7A, TH and EVC2 in two Pakistani brothers with familial deafness

Cited by 6 publications

References 25 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

High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma

Association between Aldosterone Synthase (CYP11B2) Gene Polymorphism and Hypertension in Pashtun Ethnic Population of Khyber Pakhtunkwha, Pakistan

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