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Genetic Epidemiology of Deafness

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (1 August 2019) | Viewed by 49189

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Special Issue Editors

Prof. Dr. Shin-ichi Usami

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Guest Editor

Department of Otorhinolaryngology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Interests: hearing; cochlear implantation; molecular genetics; genetic testing; phylogenetics

Prof. Karen B. Avraham

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Guest Editor

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo 6997801, Israel
Interests: deafness; inner ear; genetics; transcriptome; microRNAs; lncRNAs; methylation

Prof. Dr. Richard J. H. Smith

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Guest Editor

Department of Otolaryngology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA
Interests: human genetics; deafness; gene therapy

Special Issue Information

Hearing impairment is a disorder with high genetic heterogeneity, and over the past two decades extreme progress has been made in identifying many different responsible genes. The identification of deafness-causing genes has shed light on the biology of hearing and genetic testing has become an indispensable diagnostic tool for personalized therapeutic intervention for deafness patients.

Knowledge of genomic variations responsible for deafness has been accumulated through extensive sequencing data using next-generation sequencing.

To date, more than one hundred deafness genes have been identified, and the genetic epidemiology of deafness has become clearer. This special issue is a collection of excellent papers providing an overview of current knowledge on 1) genetic epidemiology, 2) different mutation spectra based on different ethnic backgrounds, 3) haplotype analysis of particular deafness-causing genes, 4) origins of gene mutations and human migration, 5) case reports or case series associated with ethnic specific gene mutations (a description that it is ethnic-specific with respect to that mutation is necessary), 6) genetic background of patients receiving cochlear implantation, and 7) mutation screening strategies based on ethnicity.

Prof. Shin-ichi Usami
Prof. Karen B. Avraham
Prof. Richard J. H. Smith
Guest Editors

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Keywords

Deafness
Mutation spectrum
Epidemiology
Ethnicity
Recurrent mutation
Haplotype analysis
Common ancestor
Next generation sequencing
Mutation screening
Cochlear implantation

Published Papers (13 papers)

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14 pages, 1930 KiB

Open AccessFeature PaperArticle

Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-onset Progressive Hearing Loss

by Shin-ichiro Oka, Timothy F. Day, Shin-ya Nishio, Hideaki Moteki, Maiko Miyagawa, Shinya Morita, Shuji Izumi, Tetsuo Ikezono, Satoko Abe, Jun Nakayama, Misako Hyogo, Nobuhiko Okamoto, Natsumi Uehara, Chie Oshikawa, Shin-ichiro Kitajiri and Shin-ichi Usami

Genes 2020, 11(3), 273; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11030273 - 04 Mar 2020

Cited by 13 | Viewed by 3214

Abstract

MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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9 pages, 975 KiB

Open AccessArticle

Haplotype Analysis of GJB2 Mutations: Founder Effect or Mutational Hot Spot?

by Jun Shinagawa, Hideaki Moteki, Shin-ya Nishio, Yoshihiro Noguchi and Shin-ichi Usami

Genes 2020, 11(3), 250; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11030250 - 27 Feb 2020

Cited by 19 | Viewed by 3423

Abstract

The GJB2 gene is the most frequent cause of congenital or early onset hearing loss worldwide. In this study, we investigated the haplotypes of six GJB2 mutations frequently observed in Japanese hearing loss patients (i.e., c.235delC, p.V37I, p.[G45E; Y136X], p.R143W, c.176_191del, and c.299_300delAT) and analyzed whether the recurring mechanisms for each mutation are due to founder effects or mutational hot spots. Furthermore, regarding the mutations considered to be caused by founder effects, we also calculated the age at which each mutation occurred using the principle of genetic clock analysis. As a result, all six mutations were observed in a specific haplotype and were estimated to derive from founder effects. Our haplotype data together with their distribution patterns indicated that p.R143W and p.V37I may have occurred as multiple events, and suggested that both a founder effect and hot spot may be involved in some mutations. With regard to the founders’ age of frequent GJB2 mutations, each mutation may have occurred at a different time, with the oldest, p.V37I, considered to have occurred around 14,500 years ago, and the most recent, c.176_191del, considered to have occurred around 4000 years ago. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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11 pages, 1869 KiB

Open AccessArticle

Enhancing Genetic Medicine: Rapid and Cost-Effective Molecular Diagnosis for a GJB2 Founder Mutation for Hearing Impairment in Ghana

by Samuel M. Adadey, Edmond Tingang Wonkam, Elvis Twumasi Aboagye, Darius Quansah, Adwoa Asante-Poku, Osbourne Quaye, Geoffrey K. Amedofu, Gordon A. Awandare and Ambroise Wonkam

Genes 2020, 11(2), 132; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11020132 - 27 Jan 2020

Cited by 6 | Viewed by 3284

Abstract

In Ghana, gap-junction protein β 2 (GJB2) variants account for about 25.9% of familial hearing impairment (HI) cases. The GJB2-p.Arg143Trp (NM_004004.6:c.427C>T/OMIM: 121011.0009/rs80338948) variant remains the most frequent variant associated with congenital HI in Ghana, but has not yet been investigated in clinical practice. We therefore sought to design a rapid and cost-effective test to detect this variant. We sampled 20 hearing-impaired and 10 normal hearing family members from 8 families segregating autosomal recessive non syndromic HI. In addition, a total of 111 unrelated isolated individuals with HI were selected, as well as 50 normal hearing control participants. A restriction fragment length polymorphism (RFLP) test was designed, using the restriction enzyme NciI optimized and validated with Sanger sequencing, for rapid genotyping of the common GJB2-p.Arg143Trp variant. All hearing-impaired participants from 7/8 families were homozygous positive for the GJB2-p.Arg143Trp mutation using the NciI-RFLP test, which was confirmed with Sanger sequencing. The investigation of 111 individuals with isolated non-syndromic HI that were previously Sanger sequenced found that the sensitivity of the GJB2-p.Arg143Trp NciI-RFLP testing was 100%. All the 50 control subjects with normal hearing were found to be negative for the variant. Although the test is extremely valuable, it is not 100% specific because it cannot differentiate between other mutations at the recognition site of the restriction enzyme. The GJB2-p.Arg143Trp NciI-RFLP-based diagnostic test had a high sensitivity for genotyping the most common GJB2 pathogenic and founder variant (p.Arg143Trp) within the Ghanaian populations. We recommend the adoption and implementation of this test for hearing impairment genetic clinical investigations to complement the newborn hearing screening program in Ghana. The present study is a practical case scenario of enhancing genetic medicine in Africa. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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14 pages, 4642 KiB

Open AccessArticle

The Hearing Impairment Ontology: A Tool for Unifying Hearing Impairment Knowledge to Enhance Collaborative Research

by Jade Hotchkiss, Noluthando Manyisa, Samuel Mawuli Adadey, Oluwafemi Gabriel Oluwole, Edmond Wonkam, Khuthala Mnika, Abdoulaye Yalcouye, Victoria Nembaware, Melissa Haendel, Nicole Vasilevsky, Nicola J. Mulder, Simon Jupp, Ambroise Wonkam and Gaston K. Mazandu

Genes 2019, 10(12), 960; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10120960 - 21 Nov 2019

Cited by 5 | Viewed by 3261

Abstract

Hearing impairment (HI) is a common sensory disorder that is defined as the partial or complete inability to detect sound in one or both ears. This diverse pathology is associated with a myriad of phenotypic expressions and can be non-syndromic or syndromic. HI can be caused by various genetic, environmental, and/or unknown factors. Some ontologies capture some HI forms, phenotypes, and syndromes, but there is no comprehensive knowledge portal which includes aspects specific to the HI disease state. This hampers inter-study comparability, integration, and interoperability within and across disciplines. This work describes the HI Ontology (HIO) that was developed based on the Sickle Cell Disease Ontology (SCDO) model. This is a collaboratively developed resource built around the ‘Hearing Impairment’ concept by a group of experts in different aspects of HI and ontologies. HIO is the first comprehensive, standardized, hierarchical, and logical representation of existing HI knowledge. HIO allows researchers and clinicians alike to readily access standardized HI-related knowledge in a single location and promotes collaborations and HI information sharing, including epidemiological, socio-environmental, biomedical, genetic, and phenotypic information. Furthermore, this ontology illustrates the adaptability of the SCDO framework for use in developing a disease-specific ontology. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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9 pages, 1312 KiB

Open AccessArticle

GJB2 and GJB6 Mutations in Hereditary Recessive Non-Syndromic Hearing Impairment in Cameroon

by Edmond Tingang Wonkam, Emile Chimusa, Jean Jacques Noubiap, Samuel Mawuli Adadey, Jean Valentin F. Fokouo and Ambroise Wonkam

Genes 2019, 10(11), 844; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10110844 - 25 Oct 2019

Cited by 17 | Viewed by 3717

Abstract

This study aimed to investigate GJB2 (connexin 26) and GJB6 (connexin 30) mutations associated with familial non-syndromic childhood hearing impairment (HI) in Cameroon. We selected only families segregating HI, with at least two affected individuals and with strong evidence of non-environmental causes. DNA was extracted from peripheral blood, and the entire coding region of GJB2 was interrogated using Sanger sequencing. Multiplex PCR and Sanger sequencing were used to analyze the prevalence of the GJB6-D3S1830 deletion. A total of 93 patients, belonging to 41 families, were included in the analysis. Hearing impairment was sensorineural in 51 out of 54 (94.4%) patients. Pedigree analysis suggested autosomal recessive inheritance in 85.4% (35/41) of families. Hearing impairment was inherited in an autosomal dominant and mitochondrial mode in 12.2% (5/41) and 2.4% (1/41) of families, respectively. Most HI participants were non-syndromic (92.5%; 86/93). Four patients from two families presented with type 2 Waardenburg syndrome, and three cases of type 2 Usher syndrome were identified in one family. No GJB2 mutations were found in any of the 29 families with non-syndromic HI. Additionally, the GJB6-D3S1830 deletion was not identified in any of the HI patients. This study confirms that mutations in the GJB2 gene and the del(GJB6-D13S1830) mutation do not contribute to familial HI in Cameroon. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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20 pages, 861 KiB

Open AccessArticle

Genetic Epidemiology and Clinical Features of Hereditary Hearing Impairment in the Taiwanese Population

by Chen-Chi Wu, Cheng-Yu Tsai, Yi-Hsin Lin, Pey-Yu Chen, Pei-Hsuan Lin, Yen-Fu Cheng, Che-Ming Wu, Yin-Hung Lin, Chee-Yee Lee, Jargalkhuu Erdenechuluun, Tien-Chen Liu, Pei-Lung Chen and Chuan-Jen Hsu

Genes 2019, 10(10), 772; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100772 - 01 Oct 2019

Cited by 31 | Viewed by 4849

Abstract

Hereditary hearing impairment (HHI) is a common but heterogeneous clinical entity caused by mutations in a plethora of deafness genes. Research over the past few decades has shown that the genetic epidemiology of HHI varies significantly across populations. In this study, we used different genetic examination strategies to address the genetic causes of HHI in a large Taiwanese cohort composed of >5000 hearing-impaired families. We also analyzed the clinical features associated with specific genetic mutations. Our results demonstrated that next-generation sequencing-based examination strategies could achieve genetic diagnosis in approximately half of the families. Common deafness-associated genes in the Taiwanese patients assessed, in the order of prevalence, included GJB2, SLC26A4, OTOF, MYO15A, and MTRNR1, which were similar to those found in other populations. However, the Taiwanese patients had some unique mutations in these genes. These findings may have important clinical implications for refining molecular diagnostics, facilitating genetic counseling, and enabling precision medicine for the management of HHI. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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17 pages, 3373 KiB

Open AccessArticle

The Prevalence and Clinical Characteristics of TECTA-Associated Autosomal Dominant Hearing Loss

by Rika Yasukawa, Hideaki Moteki, Shin-ya Nishio, Kotaro Ishikawa, Satoko Abe, Yohei Honkura, Misako Hyogo, Ryota Mihashi, Tetsuo Ikezono, Tomoko Shintani, Noriko Ogasawara, Kyoko Shirai, Hiroshi Yoshihashi, Takashi Ishino, Koshi Otsuki, Tsukasa Ito, Kazuma Sugahara and Shin-ichi Usami

Genes 2019, 10(10), 744; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100744 - 24 Sep 2019

Cited by 16 | Viewed by 3560

Abstract

TECTA is well known as a causative gene for autosomal dominant mid-frequency hearing loss observed in various populations. In this study, we performed next-generation sequencing analysis of a large Japanese hearing loss cohort, including eight hundred and twelve (812) subjects from unrelated autosomal dominant hearing loss families, to estimate the prevalence and phenotype-genotype correlations in patients with TECTA mutations. The prevalence of TECTA mutations in Japanese autosomal dominant sensorineural hearing loss families was found to be 3.2%. With regard to the type of hearing loss, the patients with mutations in the nidogen-like domain or ZA domain of TECTA showed varied audiograms. However, most of the patients with mutations in the ZP domain showed mid-frequency hearing loss. The rate of hearing deterioration in TECTA-associated hearing loss patients and in the normal hearing Japanese control population were the same and regression lines for each group were parallel. We carried out haplotype analysis for four families which had one recurring missense variant, c.5597C>T (p.Thr1866Met). Our results revealed four different haplotypes, suggesting that this mutation occurred independently in each family. In conclusion, TECTA variants represent the second largest cause of autosomal dominant sensorineural hearing loss in Japan. The hearing loss progression observed in the patients with TECTA mutations might reflect presbycusis. The c.5597C>T mutation occurred in a mutational hot spot and is observed in many ethnic populations. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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20 pages, 6483 KiB

Open AccessArticle

Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort

by Karuna Maekawa, Shin-ya Nishio, Satoko Abe, Shin-ichi Goto, Yohei Honkura, Satoshi Iwasaki, Yukihiko Kanda, Yumiko Kobayashi, Shin-ichiro Oka, Mayuri Okami, Chie Oshikawa, Naoko Sakuma, Hajime Sano, Masayuki Shirakura, Natsumi Uehara and Shin-ichi Usami

Genes 2019, 10(10), 735; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10100735 - 23 Sep 2019

Cited by 14 | Viewed by 3390

Abstract

Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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17 pages, 1061 KiB

Open AccessArticle

Mid-Frequency Hearing Loss Is Characteristic Clinical Feature of OTOA-Associated Hearing Loss

by Kenjiro Sugiyama, Hideaki Moteki, Shin-ichiro Kitajiri, Tomohiro Kitano, Shin-ya Nishio, Tomomi Yamaguchi, Keiko Wakui, Satoko Abe, Akiko Ozaki, Remi Motegi, Hirooki Matsui, Masato Teraoka, Yumiko Kobayashi, Tomoki Kosho and Shin-ichi Usami

Genes 2019, 10(9), 715; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10090715 - 16 Sep 2019

Cited by 15 | Viewed by 4540

Abstract

The OTOA gene (Locus: DFNB22) is reported to be one of the causative genes for non-syndromic autosomal recessive hearing loss. The copy number variations (CNVs) identified in this gene are also known to cause hearing loss, but have not been identified in Japanese patients with hearing loss. Furthermore, the clinical features of OTOA-associated hearing loss have not yet been clarified. In this study, we performed CNV analyses of a large Japanese hearing loss cohort, and identified CNVs in 234 of 2262 (10.3%, 234/2262) patients with autosomal recessive hearing loss. Among the identified CNVs, OTOA gene-related CNVs were the second most frequent (0.6%, 14/2262). Among the 14 cases, 2 individuals carried OTOA homozygous deletions, 4 carried heterozygous deletions with single nucleotide variants (SNVs) in another allele. Additionally, 1 individual with homozygous SNVs in the OTOA gene was also identified. Finally, we identified 7 probands with OTOA-associated hearing loss, so that its prevalence in Japanese patients with autosomal recessive hearing loss was calculated to be 0.3% (7/2262). As novel clinical features identified in this study, the audiometric configurations of patients with OTOA-associated hearing loss were found to be mid-frequency. This is the first study focused on the detailed clinical features of hearing loss caused by this gene mutation and/or gene deletion. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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10 pages, 964 KiB

Open AccessArticle

Identification of Main Genetic Causes Responsible for Non-Syndromic Hearing Loss in a Peruvian Population

by Erick Figueroa-Ildefonso, Guney Bademci, Farid Rajabli, Mario Cornejo-Olivas, Ruy Diego Chacón Villanueva, Rodolfo Badillo-Carrillo, Miguel Inca-Martinez, Karina Milla Neyra, Claire Sineni and Mustafa Tekin

Genes 2019, 10(8), 581; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10080581 - 31 Jul 2019

Cited by 5 | Viewed by 3667

Abstract

Hearing loss (HL) is a common sensory disorder affecting over 5% of the global population. The etiology underlying HL includes congenital and acquired causes; genetic factors are the main cause in over 50% of congenital cases. Pathogenic variants in the GJB2 gene are a major cause of congenital non-syndromic hearing loss (NSHL), while their distribution is highly heterogeneous in different populations. To the best of our knowledge, there is no data regarding the genetic etiologies of HL in Peru. In this study, we screened 133 Peruvian families with NSHL living in Lima. We sequenced both exons of the GJB2 gene for all probands. Seven probands with familial NSHL that remained negative for GJB2 variants underwent whole genome sequencing (WGS). We identified biallelic pathogenic variants in GJB2 in 43 probands; seven were heterozygous for only one allele. The c.427C>T variant was the most common pathogenic variant followed by the c.35delG variant. WGS revealed three novel variants in MYO15A in two probands, one of them was predicted to affect splicing and the others produce a premature stop codon. The Peruvian population showed a complex profile for genetic variants in the GJB2 gene, this particular profile might be a consequence of the admixture history in Peru. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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14 pages, 10926 KiB

Open AccessArticle

Three New Mutations and Mild, Asymmetrical Phenotype in the Highly Distinctive LAMM Syndrome: A Report of Eight Further Cases

by Amina Al Yassin, Felice D’Arco, Matías Morín, Waheeda Pagarkar, Katherine Harrop-Griffiths, Azhar Shaida, Elena Fernández, Tom Cullup, Bianca De-Souza, Miguel Angel Moreno-Pelayo and Maria Bitner-Glindzicz

Genes 2019, 10(7), 529; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10070529 - 12 Jul 2019

Cited by 8 | Viewed by 3346

Abstract

Labyrinthine aplasia, microtia, and microdontia (LAMM) is an autosomal recessive condition causing profound congenital deafness, complete absence of inner ear structures (usually Michel’s aplasia), microtia (usually type 1) and microdontia. To date, several families have been described with this condition and a number of mutations has been reported. We report on eight further cases of LAMM syndrome including three novel mutations, c. 173T>C p.L58P; c. 284G>A p.(Arg95Gln) and c.325_327delinsA p.(Glu109Thrfs*18). Congenital deafness was the primary presenting feature in all affected individuals and consanguinity in all but two families. We compare the features in our patients to those previously reported in LAMM, and describe a milder, asymmetrical phenotype associated with FGF3 mutations. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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17 pages, 1313 KiB

Open AccessArticle

Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys)

by Olga L. Posukh, Marina V. Zytsar, Marita S. Bady-Khoo, Valeria Yu. Danilchenko, Ekaterina A. Maslova, Nikolay A. Barashkov, Alexander A. Bondar, Igor V. Morozov, Vladimir N. Maximov and Michael I. Voevoda

Genes 2019, 10(6), 429; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10060429 - 05 Jun 2019

Cited by 13 | Viewed by 3789

Abstract

Mutations in the GJB2 gene are the main cause for nonsyndromic autosomal recessive deafness 1A (DFNB1A) in many populations. GJB2 mutational spectrum and pathogenic contribution are widely varying in different populations. Significant efforts have been made worldwide to define DFNB1A molecular epidemiology, but this issue still remains open for some populations. The main aim of study is to estimate the DFNB1A prevalence and GJB2 mutational spectrum in Tuvinians—an indigenous population of the Tyva Republic (Southern Siberia, Russia). Sanger sequencing was applied to analysis of coding (exon 2) and non-coding regions of GJB2 in a cohort of Tuvinian patients with hearing impairments (n = 220) and ethnically matched controls (n = 157). Diagnosis of DFNB1A was established for 22.3% patients (28.8% of familial vs 18.6% of sporadic cases). Our results support that patients with monoallelic GJB2 mutations (8.2%) are coincidental carriers. Recessive mutations p.Trp172Cys, c.-23+1G>A, c.235delC, c.299_300delAT, p.Val37Ile and several benign variants were found in examined patients. A striking finding was a high prevalence of rare variant p.Trp172Cys (c.516G>C) in Tuvinians accounting for 62.9% of all mutant GJB2 alleles and a carrier frequency of 3.8% in controls. All obtained data provide important targeted information for genetic counseling of affected Tuvinian families and enrich current information on variability of GJB2 worldwide. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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Hearing Impairment Overview in Africa: the Case of Cameroon

by Edmond Wonkam Tingang, Jean Jacques Noubiap, Jean Valentin F. Fokouo, Oluwafemi Gabriel Oluwole, Séraphin Nguefack, Emile R. Chimusa and Ambroise Wonkam

Genes 2020, 11(2), 233; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11020233 - 22 Feb 2020

Cited by 14 | Viewed by 4213

Abstract

The incidence of hearing impairment (HI) is higher in low- and middle-income countries when compared to high-income countries. There is therefore a necessity to estimate the burden of this condition in developing world. The aim of our study was to use a systematic approach to provide summarized data on the prevalence, etiologies, clinical patterns and genetics of HI in Cameroon. We searched PubMed, Scopus, African Journals Online, AFROLIB and African Index Medicus to identify relevant studies on HI in Cameroon, published from inception to 31 October, 2019, with no language restrictions. Reference lists of included studies were also scrutinized, and data were summarized narratively. This study is registered with PROSPERO, number CRD42019142788. We screened 333 records, of which 17 studies were finally included in the review. The prevalence of HI in Cameroon ranges from 0.9% to 3.6% in population-based studies and increases with age. Environmental factors contribute to 52.6% to 62.2% of HI cases, with meningitis, impacted wax and age-related disorder being the most common ones. Hereditary HI comprises 0.8% to 14.8% of all cases. In 32.6% to 37% of HI cases, the origin remains unknown. Non-syndromic hearing impairment (NSHI) is the most frequent clinical entity and accounts for 86.1% to 92.5% of cases of HI of genetic origin. Waardenburg and Usher syndromes account for 50% to 57.14% and 8.9% to 42.9% of genetic syndromic cases, respectively. No pathogenic mutation was described in GJB6 gene, and the prevalence of pathogenic mutations in GJB2 gene ranged from 0% to 0.5%. The prevalence of pathogenic mutations in other known NSHI genes was <10% in Cameroonian probands. Environmental factors are the leading etiology of HI in Cameroon, and mutations in most important HI genes are infrequent in Cameroon. Whole genome sequencing therefore appears as the most effective way to identify variants associated with HI in Cameroon and sub-Saharan Africa in general. Full article

(This article belongs to the Special Issue Genetic Epidemiology of Deafness)

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