scholarly journals Non-Syndromic Autosomal Dominant Hearing Loss: The First Italian Family Carrying a Mutation in the NCOA3 Gene

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1043
Author(s):  
Paola Tesolin ◽  
Anna Morgan ◽  
Michela Notarangelo ◽  
Rocco Pio Ortore ◽  
Maria Pina Concas ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Autosomal Dominant ◽  
Age Of Onset ◽  
Clinical Phenotype ◽  
Profound Hearing Loss ◽  
Live Births ◽  
Italian Family ◽  
New Gene ◽  
Syndromic Hearing Loss

Hearing loss (HL) is the most frequent sensory disorder, affecting about 1–3 per 1000 live births, with more than half of the cases attributable to genetic causes. Despite the fact that many HL causative genes have already been identified, current genetic tests fail to provide a diagnosis for about 40% of the patients, suggesting that other causes still need to be discovered. Here, we describe a four-generation Italian family affected by autosomal dominant non-syndromic hearing loss (ADNSHL), in which exome sequencing revealed a likely pathogenic variant in NCOA3 (NM_181659.3, c.2909G>C, p.(Gly970Ala)), a gene recently described as a novel candidate for ADNSHL in a Brazilian family. A comparison between the two families highlighted a series of similarities: both the identified variants are missense, localized in exon 15 of the NCOA3 gene and lead to a similar clinical phenotype, with non-syndromic, sensorineural, bilateral, moderate to profound hearing loss, with a variable age of onset. Our findings (i.e., the identification of the second family reported globally with HL caused by a variant in NCOA3) further support the involvement of NCOA3 in the etiopathogenesis of ADNSHL, which should, thus, be considered as a new gene for autosomal dominant non-syndromic hearing loss.

scholarly journals Benefits of Exome Sequencing in Children with Suspected Isolated Hearing Loss

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1277
Author(s):  
Roxane Van Heurck ◽  
Maria Teresa Carminho-Rodrigues ◽  
Emmanuelle Ranza ◽  
Caterina Stafuzza ◽  
Lina Quteineh ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Autosomal Dominant ◽  
Diagnostic Yield ◽  
Autosomal Recessive Inheritance ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Syndromic Hearing Loss ◽  
Children With Hearing Loss

Purpose: Hearing loss is characterized by an extensive genetic heterogeneity and remains a common disorder in children. Molecular diagnosis is of particular benefit in children, and permits the early identification of clinically-unrecognized hearing loss syndromes, which permits effective clinical management and follow-up, including genetic counselling. Methods: We performed whole-exome sequencing with the analysis of a panel of 189 genes associated with hearing loss in a prospective cohort of 61 children and 9 adults presenting mainly with isolated hearing loss. Results: The overall diagnostic rate using exome sequencing was 47.2% (52.5% in children; 22% in adults). In children with confirmed molecular results, 17/32 (53.2%) showed autosomal recessive inheritance patterns, 14/32 (43.75%) showed an autosomal dominant condition, and one case had X-linked hearing loss. In adults, the two patients showed an autosomal dominant inheritance pattern. Among the 32 children, 17 (53.1%) had nonsyndromic hearing loss and 15 (46.7%) had syndromic hearing loss. One adult was diagnosed with syndromic hearing loss and one with nonsyndromic hearing loss. The most common causative genes were STRC (5 cases), GJB2 (3 cases), COL11A1 (3 cases), and ACTG1 (3 cases). Conclusions: Exome sequencing has a high diagnostic yield in children with hearing loss and can reveal a syndromic hearing loss form before other organs/systems become involved, allowing the surveillance of unrecognized present and/or future complications associated with these syndromes.

scholarly journals Exome Sequencing Identifies a Mutation in EYA4 as a Novel Cause of Autosomal Dominant Non-Syndromic Hearing Loss

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126602 ◽  
Author(s):  
Fei Liu ◽  
Jiongjiong Hu ◽  
Wenjun Xia ◽  
Lili Hao ◽  
Jing Ma ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Autosomal Dominant ◽  
Syndromic Hearing Loss

SLC12A2: a new gene associated with autosomal dominant Non-Syndromic hearing loss in humans

2020 ◽  
Vol 18 (2) ◽  
pp. 149-151
Author(s):  
A. Morgan ◽  
G. Pelliccione ◽  
U. Ambrosetti ◽  
D. Dell’Orco ◽  
G. Girotto
Keyword(s):  
Hearing Loss ◽  
Autosomal Dominant ◽  
New Gene ◽  
Syndromic Hearing Loss

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.

scholarly journals TBL1Y: a new gene involved in syndromic hearing loss

2018 ◽  
Vol 27 (3) ◽  
pp. 466-474 ◽  
Author(s):  
Mariateresa Di Stazio ◽  
Chiara Collesi ◽  
Diego Vozzi ◽  
Wei Liu ◽  
Mike Myers ◽  
...  
Keyword(s):  
Hearing Loss ◽  
New Gene ◽  
Syndromic Hearing Loss

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.

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