scholarly journals Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistan families

2019 ◽  
Author(s):  
Yingjie Zhou ◽  
Muhammad Tariq ◽  
Sijie He ◽  
Uzma Abdullah ◽  
Jianguo Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Bioinformatics Analysis ◽  
The Other ◽  
Whole Exome ◽  
Clinical Detection ◽  
Syndromic Hearing Loss ◽  
Sensory Defect

Abstract Background: Hearing loss is the most common sensory defect that affects over 6% of the population worldwide. About 50%-60% of hearing loss patients are attributed to genetic causes. Currently more than 100 genes have been reported to cause non-syndromic hearing loss. It’s possible and efficient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES).Methods: We collected 5 consanguineous pedigrees with hearing loss from Pakistan and applied WES on selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causing genes for them.Results: Variants in 7 genes were identified and validated in these pedigrees. We identified single candidate for 3 pedigrees, which were GIPC3 (c.937T>C), LOXHD1 (c.2935G>A) and TMPRSS3 (c.941T>C). And the remaining 2 pedigrees each contained two candidates, which were TECTA (c.4045G>A) and MYO15A (c.3310G>T and c.1705G>C) for one pedigree and DFNB59 (c.494G>A) and TRIOBP (c.1952C>T) for the other pedigree. The candidates were validated in all available samples by Sanger sequencing.Conclusion: The candidate variants in hearing loss genes were validated to be co-segregated in the pedigrees, which may indicate the reasons for such patients. We also suggested that WES may be suitable strategy for hearing loss gene screening in clinical detection.

scholarly journals Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistan families

2020 ◽  
Author(s):  
Yingjie Zhou ◽  
Muhammad Tariq ◽  
Sijie He(Former Corresponding Author) ◽  
Uzma Abdullah ◽  
Jianguo Zhang(New Corresponding Author) ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Bioinformatics Analysis ◽  
The Other ◽  
Whole Exome ◽  
Clinical Detection ◽  
Syndromic Hearing Loss ◽  
Sensory Defect

Abstract Background Hearing loss is the most common sensory defect that affects over 6% of the population worldwide. About 50%-60% of hearing loss patients are attributed to genetic causes. Currently more than 100 genes have been reported to cause non-syndromic hearing loss. It’s possible and efficient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES). Methods We collected 5 consanguineous pedigrees with hearing loss from Pakistan and applied WES on selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causing genes for them. Results Variants in 7 genes were identified and validated in these pedigrees. We identified single candidate for 3 pedigrees, which were GIPC3 (c.937T>C), LOXHD1 (c.2935G>A) and TMPRSS3 (c.941T>C). And the remaining 2 pedigrees each contained two candidates, which were TECTA (c.4045G>A) and MYO15A (c.3310G>T and c.1705G>C) for one pedigree and DFNB59 (c.494G>A) and TRIOBP (c.1952C>T) for the other pedigree. The candidates were validated in all available samples by Sanger sequencing. Conclusion The candidate variants in hearing loss genes were validated to be co-segregated in the pedigrees, which may indicate the reasons for such patients. We also suggested that WES may be suitable strategy for hearing loss screening in clinical detection.

scholarly journals Whole exome sequencing identified mutations causing hearing loss in five consanguineous Pakistani families

2020 ◽  
Author(s):  
Yingjie Zhou ◽  
Muhammad Tariq ◽  
Sijie He ◽  
Uzma Abdullah ◽  
Jianguo Zhang ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Bioinformatics Analysis ◽  
Whole Exome ◽  
Causal Genes ◽  
Clinical Detection ◽  
Syndromic Hearing Loss ◽  
Sensory Defect ◽  
Pakistani Families

Abstract Background: Hearing loss is the most common sensory defect, and it affects over 6% of the population worldwide. Approximately 50%-60% of hearing loss patients are attributed to genetic causes. Currently, more than 100 genes have been reported to cause non-syndromic hearing loss. It is possible and efficient to screen all potential disease-causing genes for hereditary hearing loss by whole exome sequencing (WES).Methods: We collected 5 consanguineous pedigrees from Pakistan with hearing loss and applied WES in selected patients for each pedigree, followed by bioinformatics analysis and Sanger validation to identify the causal genes.Results: Variants in 7 genes were identified and validated in these pedigrees. We identified single candidate variant for 3 pedigrees: GIPC3 (c.937T>C), LOXHD1 (c.6136G>A) and TMPRSS3 (c.941T>C). The remaining 2 pedigrees each contained two candidate variants: TECTA (c.4045G>A) and MYO15A (c.3310G>T and c.9913G>C) for one pedigree and DFNB59 (c.494G>A) and TRIOBP (c.1952C>T) for the other pedigree. The candidate variants were validated in all available samples by Sanger sequencing.Conclusion: The candidate variants in hearing-loss genes were validated to be co-segregated in the pedigrees, and they may indicate the aetiologies of hearing loss in such patients. We also suggest that WES may be a suitable strategy for hearing-loss gene screening in clinical detection.

Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

2020 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

Whole Exome Sequencing of Six Chinese Families with Hereditary Non-syndromic Hearing Loss

2021 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results:Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions:Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

scholarly journals Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Somayeh Khatami ◽  
Masomeh Askari ◽  
Fatemeh Bahreini ◽  
Morteza Hashemzadeh-Chaleshtori ◽  
Saeed Hematian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Diagnosis ◽  
Clinical Genetic ◽  
Large Size ◽  
Whole Exome ◽  
Novel Variants ◽  
Syndromic Hearing Loss ◽  
Traditional Approaches

Abstract Background Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. Methods This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. Results The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. Conclusion In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

Whole exome sequencing of six Chinese families with hereditary non-syndromic hearing loss

2021 ◽  
pp. 110817
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Whole exome sequencing identifies both nuclear and mitochondrial variations in an Iranian family with non-syndromic hearing loss

Mitochondrion ◽  
2019 ◽  
Vol 46 ◽  
pp. 321-325 ◽  
Author(s):  
Somayeh Khatami ◽  
Hassan Rokni-Zadeh ◽  
Neda Mohsen-Pour ◽  
Alireza Biglari ◽  
Majid Changi-Ashtiani ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Whole Exome ◽  
Iranian Family ◽  
Syndromic Hearing Loss

scholarly journals Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guangxian Yang ◽  
Yi Yin ◽  
Zhiping Tan ◽  
Jian Liu ◽  
Xicheng Deng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Renal Malformations

Abstract Background Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. Methods A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. Results Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. Conclusions This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

scholarly journals Whole-Exome Sequencing Reveals a Rare Variant of OTOF Gene Causing Congenital Non-syndromic Hearing Loss Among Large Muslim Families Favoring Consanguinity

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohd Fareed ◽  
Varun Sharma ◽  
Inderpal Singh ◽  
Sayeed Ur Rehman ◽  
Gurdarshan Singh ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Disease Risk ◽  
New Delhi ◽  
Homozygous Mutation ◽  
Jammu And Kashmir ◽  
Whole Exome ◽  
Recurrent Mutations ◽  
Syndromic Hearing Loss

Non-syndromic hearing loss (NSHL) is one of the most frequent auditory deficits in humans characterized by high clinical and genetic heterogeneity. Very few studies have reported the relationship between OTOF (Locus: DFNB9) and hereditary hearing loss in India. We aimed to decipher the genetic cause of prelingual NSHL in a large affected Muslim consanguineous families using whole-exome sequencing (WES). The study was performed following the guidelines and regulations of the Indian Council of Medical Research (ICMR), New Delhi. The population was identified from Jammu and Kashmir, the Northernmost part of India. Near about 100 individuals were born deaf-mute in the village of 3,000 inhabitants. A total of 103 individuals (with 52 cases and 51 controls) agreed to participate in this study. Our study revealed a rare non-sense homozygous mutation NC_000002.11:g.2:26702224G>A; NM_001287489.2:c.2122C>T; NP_001274418.1:p.(Arg708∗) in the 18th exon of the OTOF gene. Our study provides the first insight into this homozygous condition, which has not been previously reported in ExAC, 1,000 Genome and genomAD databases. Furthermore, the variant was confirmed in the population cohort (n = 103) using Sanger sequencing. In addition to the pathogenic OTOF variant, the WES data also revealed novel and recurrent mutations in CDH23, GJB2, MYO15A, OTOG, and SLC26A4 genes. The rare pathogenic and the novel variants observed in this study have been submitted to the ClinVar database and are publicly available online with the accessions SCV001448680.1, SCV001448682.1 and SCV001448681.1. We conclude that OTOF-related NSHL hearing loss is prevalent in the region due to successive inbreeding in its generations. We recommend premarital genetic testing and genetic counseling strategies to minimize and control the disease risk in future generations.

Spectrum and frequencies of non GJB2 gene mutations in Czech patients with early non‐syndromic hearing loss detected by gene panel NGS and whole‐exome sequencing

2020 ◽  
Vol 98 (6) ◽  
pp. 548-554
Author(s):  
Dana Safka Brozkova ◽  
Simona Poisson Marková ◽  
Anna Uhrová Mészárosová ◽  
Ján Jenčík ◽  
Vlasta Čejnová ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Gene Mutations ◽  
Gene Panel ◽  
Gjb2 Gene ◽  
Whole Exome ◽  
Syndromic Hearing Loss
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