Deaf Families Research Articles

A novel mutation in TRIOBP gene leading to congenital deafness in a Chinese family

BackgroundThe autosomal recessive non-syndromic deafness DFNB28 is characterized by prelingual sensorineural hearing loss. The disease is related with mutations in TRIOBP (Trio- and F-actin-Binding Protein) gene, which has three transcripts referred to as TRIOBP-5, TRIOBP − 4 and TRIOBP-1. Among them, TRIOBP-5/− 4 are expressed in the inner ears and crucial for maintaining the structure and function of the stereocilia.MethodsThe proband is a 26-year-old Chinese female. She and her younger brother have being suffered from severe deafness since birth, whereas her parents, who are cousins, have normal communication ability. Hearing impairment of the two siblings was determined by pure tone audiometry. Whole Exome Sequencing (WES) was performed on the genomic DNA of the proband and Sanger sequencing was conducted on the DNA samples of the four family members.ResultsTests of pure tone hearing thresholds showed a severe to profound symmetric hearing loss for the proband and her younger brother. Moreover, a novel TRIOBP c.1342C > T (p.Arg448*) variant was identified by WES in the DNA sample of the proband and confirmed by Sanger sequencing in DNA of the family members.ConclusionsThe TRIOBP c.1342C > T (p.Arg448*) variant is predicted to disrupt TRIOBP-5 and TRIOBP-4, which may lead to the congenital deafness. The results will broaden the spectrum of pathogenic variants in TRIOBP gene. The characteristics of deafness in the family imply that marriage between close relatives should be avoided.

The p.R206C Mutation in MYO7A Leads to Autosomal Dominant Nonsyndromic Hearing Loss

Background: Dominant mutations in MYO7A may lead to nonsyndromic deafness DFNA11. A p.R206C variant in MYO7A has previously been reported in a small deaf family from Taiwan but with ambiguous pathogenicity and inheritance pattern. Aims/Objectives: Our study aims to clarify the pathogenicity of this variant by clinical characterization and genetic analysis of a separate autosomal dominant deaf family harboring this variant in mainland China. Materials and Methods: Auditory features of hearing loss were characterized in representative affected family members. Mutation screening was performed by targeted next-generation sequencing of 138 known deafness genes in the proband. Candidate pathogenic mutations were confirmed by Sanger sequencing in family members and ethnically matched controls. Results: Consistent with typical DFNA11 phenotype, the affected family members in this study showed delayed-onset, progressive hearing loss affecting mostly high frequencies. Targeted next-generation sequencing identified a p.R206C mutation in MYO7A as the only candidate pathogenic mutation cosegregating with the hearing phenotype. This mutation is not seen in 200 Chinese Han normal-hearing controls. Conclusions and Significance: The recurrent p.R206C variant in MYO7A is pathogenic and is likely in a mutation hot spot or due to a founder effect. Reports of such rare variants in multiple patients or families may facilitate exploitation of its pathogenicity.

Clinical and genetic study of 12 Chinese Han families with nonsyndromic deafness.

BackgroundNonsyndromic hearing loss is clinically and genetically heterogeneous. In this study, we characterized the clinical features of 12 Chinese Han deaf families in which mutations in common deafness genes GJB2, SLC26A4, and MT‐RNR1 were excluded.MethodsTargeted next‐generation sequencing of 147 known deafness genes was performed in probands of 10 families, while whole‐exome sequencing was applied in those of the rest two.ResultsPathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands, with 16 mutations being novel. Intrafamilial cosegregation of the mutations and the deafness phenotype were confirmed by Sanger sequencing.ConclusionOur results expanded the mutation spectrum and genotype‒phenotype correlation of nonsyndromic hearing loss in Chinese Hans and also emphasized the importance of combining both next‐generation sequencing and detailed auditory evaluation to achieve a more accurate diagnosis for nonsyndromic hearing loss.

Prelingual Sensorineural Hearing Loss Caused by a Novel GJB2 Dominant Mutation in a Chinese Family.

Background GJB2 mutation is the most common cause of genetic deafness. Many pathogenic variations have already been identified, and thus, fewer and fewer novel pathogenic variations remain to be identified. Here, we describe a novel pathogenic variation associated with dominant hereditary deafness in a Chinese family. Methods In this study, we examined four generations of a Chinese family (M127) with hearing loss. Temporal CT scan, complete physical examination (including skin and hair), and audiological tests were performed. Targeted next-generation and Sanger sequencing were used to identify pathogenic mutations in affected individuals. Results All patients exhibited prelingual nonsyndromic sensorineural hearing loss, with severity ranging from moderate to severe. A novel dominant pathogenic variant c.205T > C (p.Phe69Leu) was identified in all patients in this family. Conclusions c.205T > C (p.Phe69Leu) was identified as a novel dominant pathogenic variant of GJB2 associated with prelingual nonsyndromic sensorineural hearing loss.GJB2 mutation is the most common cause of genetic deafness. Many pathogenic variations have already been identified, and thus, fewer and fewer novel pathogenic variations remain to be identified. Here, we describe a novel pathogenic variation associated with dominant hereditary deafness in a Chinese family.

A Community-Based Participatory Research Project Involving Latino Families of Deaf and Hard-of-hearing Children

The community-based participatory research project described in this paper was designed to help Spanish-speaking families of deaf and hard-of-hearing children gain access to necessary health, education, and local resource information. The project was motivated by the need to improve communication between medical and education resource centers with Spanish-speaking families. This paper reports on the specific methods and implementation of the partnership approach, the development of the project, and lessons learned for future projects of this type.

Evidence for gene-smoking interactions for hearing loss and deafness in Japanese American families

Evidence for gene-smoking interactions for hearing loss and deafness in Japanese American families

Evidence for gene-smoking interactions for hearing loss and deafness in Japanese American families

BackgroundThis study investigated the relationship between smoking and hearing loss and deafness (HLD) and whether the relationship is modified by genetic variation. Data for these analyses was from the subset of Japanese American families collected as part of the American Diabetes Association Genetics of Non-insulin Dependent Diabetes Mellitus study. Logistic regression with generalized estimating equations assessed the relationship between HLD and smoking. Nonparametric linkage analysis identified genetic regions harboring HLD susceptibility genes and ordered subset analysis was used to identify regions showing evidence for gene-smoking interactions. Genetic variants within these candidate regions were then each tested for interaction with smoking using logistic regression models. ResultsAfter adjusting for age, sex, diabetes status and smoking duration, for each pack of cigarettes smoked per day, risk of HLD increased 4.58 times (odds ratio (OR) = 4.58; 95% Confidence Interval (CI): (1.40,15.03)), and ever smokers were over 5 times more likely than nonsmokers to report HLD (OR = 5.22; 95% CI: (1.24, 22.03)). Suggestive evidence for linkage for HLD was observed in multiple genomic regions (Chromosomes 5p15, 8p23 and 17q21), and additional suggestive regions were identified when considering interactions with smoking status (Chromosomes 7p21, 11q23, 12q32, 15q26, and 20q13) and packs-per-day (Chromosome 8q21). ConclusionsTo our knowledge this was the first report of possible gene-by-smoking interactions in HLD using family data. Additional work, including independent replication, is needed to understand the basis of these findings. HLD are important public health issues and understanding the contributions of genetic and environmental factors may inform public health messages and policies.

Spelling in Deaf, Hard of Hearing and Hearing Children With Sign Language Knowledge.

What do spelling errors look like in children with sign language knowledge but with variation in hearing background, and what strategies do these children rely on when they learn how to spell in written language? Earlier research suggests that the spelling of children with hearing loss is different, because of their lack of hearing, which requires them to rely on other strategies. In this study, we examine whether, and how, different variables such as hearing degree, sign language knowledge and bilingualism may affect the spelling strategies of children with Swedish sign language, Svenskt teckenspråk, (STS) knowledge, and whether these variables can be mirrored in these children’s spelling. The spelling process of nineteen children with STS knowledge (mean age: 10.9) with different hearing degrees, born into deaf families, is described and compared with a group of fourteen hearing children without STS knowledge (mean age: 10.9). Keystroke logging was used to investigate the participants’ writing process. The spelling behavior of the children was further analyzed and categorized into different spelling error categories. The results indicate that many children showed exceptionally few spelling errors compared to earlier studies, that may derive from their early exposure of STS, enabling them to use the fingerspelling strategy. All of the children also demonstrated similar typing skills. The deaf children showed a tendency to rely on a visual strategy during spelling, which may result in incorrect, but visually similar, words, i.e., a type of spelling errors not found in texts by hearing children with STS knowledge. The deaf children also showed direct transfer from STS in their spelling. It was found that hard-of-hearing children together with hearing children of deaf adults (CODAs), both with STS knowledge, used a sounding strategy, rather than a visual strategy. Overall, this study suggests that the ability to hear and to use sign language, together and respectively, play a significant role for the spelling patterns and spelling strategies used by the children with and without hearing loss.

Using the Adapted Flemish Sign Language Visual Communication and Sign Language Checklist.

This study addresses the topic of visual communication and early sign language acquisition in deaf children with a Flemish Sign Language (Vlaamse Gebarentaal or VGT) input. Results are obtained through a checklist focusing on sign-exposed deaf children's visual communication and early sign language acquisition: the adapted VGT Visual Communication and Sign Language checklist. The purpose is to obtain the first detailed picture of these children's visual and early VGT acquisition and to determine the optimal support for the checklist's ongoing standardization process. At the time of testing, all children were 24-months old and had been diagnosed with a severe or profound hearing loss before the age of 6months. Half of the children were being raised in deaf families with native VGT exposure, while the other half were from hearing families with no prior VGT knowledge. All parents declared VGT accessibility to the child and that they used VGT in the home. Resulting from this study is the identification of five early visual communication items as being potentially good indicators of later (sign) language development. Further, concerns were put forward on the lack of ongoing visual, communication, and language support for deaf children and their parents in Flanders.

Mutation analysis of the SLC26A4 gene in three Chinese families.

In order to investigate the genetic causes of hearing loss in a Chinese proband (in Family A) with enlarged vestibular aqueduct (EVA) and to investigate the genotype of two Chinese probands with SLC26A4 singe-allelic mutation and normal hearing (in Families B and C, respectively), the three probands and their parents were clinically and genetically evaluated. Twenty exons and flanking splice sites of the SLC26A4 gene were screened for pathogenic mutations via amplification with PCR and bidirectional sequencing. As controls, a group of 400 healthy newborns from the same ethnic background underwent SLC26A4 gene screening using the same method. The three probands all harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. The genotypes of mutations in Families A, B, and C are c.1211C>A/c.919-2A>G, c.1729G>A/c.919-2A>G, and c.1286C>A/c.919-2A>G, respectively. The missense mutations c.1211C>A (p.T430Q) in exon 10 and c.1729G>A (p.V577I) in exon 16 are both reported for the first time and were absent in 400 healthy newborns. c.1211C>A has Glutamine (Gln) at amino acid 430 instead of Threonine (Thr), and c.1729G>A has Isoleucine (Ile) at amino acid 577 instead of Valine (Val). c.1286C>A, a mutation previously reported in DVD and HGMD, was associated with Mondini deformity, but a proband with the c.1286C>A mutation in this study was normal. This study has demonstrated that the novel missense mutation c.1211C>A in compound heterozygosity with c.919-2A>G in the SLC26A4 gene is likely to be the cause of deafness in Family A. A novel variant, c.1729G>A, was identified and is likely benign. The pathogenicity of the c.1286C>A mutation warrants more in-depth study. These findings will broaden the spectrum of known SLC26A4 mutations in the Chinese population, providing more information for genetic counseling and diagnosis of hearing loss with EVA.

At the Crossroad of Cultures: Education and Identity of Hungarian Deaf Learners in Romania

Deaf people living in ethnic-national minority situation form a social group whose members have multiple cultural backgrounds. Starting from interpretations which are viewing the deaf child as a member of a distinct cultural and linguistic minority, I studied the education of Hungarian deaf pupils in Romania graduating from the Hungarian Special School in Cluj/Kolozsvár/Klausenburg, with particular regard to the relationship between formal and informal language use in school, communication culture and identity. Methodologically the research is based on life path interviews with Hungarian Deaf Special School graduates, family case studies of two or three generation deaf families and structured interviews with experienced educators. The research results reveal that the educational practice of the concerned educational institution strengthens the pupils' identity awareness and sense of belonging to the Hungarian nation in two distinct, still interconnected ways: on the one hand, through oral language acquisition, nursing the oral Hungarian language skills, and on the other hand through cultivating the Hungarian Sign Language embedded in the deaf culture within the learner community. Nowadays, the conditions and modalities of exercising this role are changing in several respects. The positive educational effects achieved so far can be reinforced and strengthened by educational policies based on the recognition and cultivation of cultural diversity, in all its complex and multifaceted manifestations, including the peculiar needs of ethnic minority deaf learners.

Profil Keluarga Tunarungu di Bungus Teluk Kabung

Every parent who has a child would want to nurture and educate him, as well as families who have limitations or have special needs, especially in deaf families, this study explains the profile of deaf families who live in the Bungung Bay Subdistrict of Kabung Bay, the family numbered seven people, among them there was a father, mother and five other children and all of them were hearing impaired, living in remote and without electricity. This family lives with various limitations, including hearing and economic limitations, they live independently and help one another. This research will reveal the family tree, faktors causing disability, environmental perception and interaction of the deaf family in the environment. This research uses a case study method with a qualitative approach. the results show that this family is a very friendly and polite family with everyone. while the faktors that cause disability are due to hereditary faktors and are supported by environmental faktors. this is because this family lives in a remote place and far from the community. people's perception of this family is very good and they communicate using oral language and gestures to everyone.

Is it ever morally permissible to select for deafness in one\u2019s child?

As reproductive genetic technologies advance, families have more options to choose what sort of child they want to have. Using preimplantation genetic diagnosis (PGD), for example, allows parents to evaluate several existing embryos before selecting which to implant via in vitro fertilization (IVF). One of the traits PGD can identify is genetic deafness, and hearing embryos are now preferentially selected around the globe using this method. Importantly, some Deaf families desire a deaf child, and PGD–IVF is also an option for them. Selection for genetic deafness, however, encounters widespread disapproval in the hearing community, including mainstream philosophy and bioethics. In this paper I apply Elizabeth Barnes’ value-neutral model of disability as mere-difference to the case of selecting for deafness. I draw on evidence from Deaf Studies and Disability Studies to build an understanding of deafness, the Deaf community, and the circumstances relevant to reproductive choices that may obtain for some Deaf families. Selection for deafness, with deafness understood as mere-difference and valued for its cultural identity, need not necessitate impermissible moral harms. I thus advocate that it is sometimes morally permissible to select for deafness in one’s child.

Non-Touch Sign Word Recognition Based on Dynamic Hand Gesture Using Hybrid Segmentation and CNN Feature Fusion

Hand gesture-based sign language recognition is a prosperous application of human– computer interaction (HCI), where the deaf community, hard of hearing, and deaf family members communicate with the help of a computer device. To help the deaf community, this paper presents a non-touch sign word recognition system that translates the gesture of a sign word into text. However, the uncontrolled environment, perspective light diversity, and partial occlusion may greatly affect the reliability of hand gesture recognition. From this point of view, a hybrid segmentation technique including YCbCr and SkinMask segmentation is developed to identify the hand and extract the feature using the feature fusion of the convolutional neural network (CNN). YCbCr performs image conversion, binarization, erosion, and eventually filling the hole to obtain the segmented images. SkinMask images are obtained by matching the color of the hand. Finally, a multiclass SVM classifier is used to classify the hand gestures of a sign word. As a result, the sign of twenty common words is evaluated in real time, and the test results confirm that this system can not only obtain better-segmented images but also has a higher recognition rate than the conventional ones.

EYA1 mutations leads to Branchio-Oto syndrome in two Chinese Han deaf families

ObjectivesBranchio-Oto (BO) syndrome is one of the common syndromic forms of hearing loss. In this study, we aimed to characterize the clinical and genetic features of BO syndrome in two Chinese Han deaf families. MethodsThe auditory and other BO-related clinical features of Family 1809 and Family 1974 were summarized. Targeted next-generation sequencing in 144 known deafness genes was performed in the probands. Co-segregation of the pathogenic mutations and the phenotype was confirmed by Sanger sequencing in the family members. ResultsInterfamilial and intrafamilial variations can be observed in the clinical phenotypes of BO syndrome in Family 1809 and 1974. A novel c.1493_1494insAT (p.Ile498PhefsTer*3) mutation and a previous reported c.967-2A>G mutation in EYA1 were identified as the pathogenic cause in Family 1974 and 1809, respectively. ConclusionOur results supported the heterogeneity of the genetic and phenotypic spectrum of BO syndrome. The recurrent c.967-2A>G in different ethnical groups suggested that it is a hot-spot mutation.

A Facebook Page Created Soon After the Amatrice Earthquake for Deaf Adults and Children, Families, and Caregivers Provides an Easy Communication Tool and Social Satisfaction in Maxi-Emergencies.

Although international and Italian conventions have issued numerous communication protocols to assist people with disabilities during earthquakes or other maxi-emergencies, no tailored strategies exist to create and disseminate information online to deaf people. On August 24, 2016, a devastating earthquake destroyed Amatrice in Central Italy. This natural disaster underlined the lack of information on disabled people possibly involved and the lack of tailored, online communication tools. Having various registries listing disabled residents in the earthquake area might have benefitted emergency procedures. To access information easily and expedite risk management, the authors developed an online information tool for deaf persons, their families, and caregivers. Within hours after the earthquake, they published a Facebook page (Facebook, Inc.; Menlo Park, California USA) including a video provided with subtitles, Italian sign language, and service numbers. Those who accessed the Facebook page spread the information to other social media. Although no registry yet specifies figures, the annual incidence of approximately three to five/1,000 new deaf persons diagnosed in Italy implies that around 5.4% of the total 43,507 Italian deaf people live in the earthquake territory, and presumably 1.3% are younger than 18 years of age. The Facebook page obtained unexpectedly numerous accesses and satisfaction from deaf adults and families with deaf children, as well as hearing family relatives and caregivers. A total of 60% deaf and 10% hearing people asked for more information. Despite limitations, the effort to develop a page for deaf people and their families, via a world-wide social media, permits fast access, outlines safety precautions during maxi-emergencies, and disseminates essential information designed for deaf people on civil protection services. The Facebook page provides a replicable example for developing similar, user-friendly, online tools for disabled groups to disseminate important safety information after earthquakes or other maxi-emergencies.Rotondi L, Zuddas M, Marsella P, Rosati P. A Facebook page created soon after the Amatrice Earthquake for deaf adults and children, families, and caregivers provides an easy communication tool and social satisfaction in maxi-emergencies. Prehosp Disaster Med. 2019;34(2):137-141.

A novel pathogenic variant in OSBPL2 linked to hereditary late-onset deafness in a Mongolian family

BackgroundTo investigate the clinical features and the underlying causal gene of a family with hereditary late-onset deafness in Inner Mongolia of China, and to provide evidence for the early genetic screening and diagnosis of this disease.MethodsFamily data were collected to draw a pedigree. Audiological testing and physical examination of the family members were conducted following questionnaire. Genomic DNA was extracted from peripheral blood of 5 family members (3 patients and 2 normal control) and subjected to whole genome sequencing for identifying deafness casual genes. The pathogenic variant in the deafness gene was further confirmed by Sanger sequencing.ResultsThe family is composed of a total of 6 generations, with 53 traceable individuals. In this family,19 of them were diagnosed with post lingual deafness with the age of onset between 10 and 40 years, displaying delayed and progressive hearing loss. Patients with hearing loss showed bilateral symmetry and mild to severe sensorineural deafness. The pattern of deafness inheritance in this family is autosomal dominant. Whole genome sequencing identified a novel pathogenic frameshift mutation, c.158_159delAA (p.Gln53Arg fs*100) in the gene OSBPL2 (Oxysterol-binding protein-related protein 2, NM_144498.2), which is absent from genomic data of 201 unrelated normal subjects. This pathogenic variant was further validated by Sanger sequencing, and was found to co-segregate in this family.ConclusionsWhole genome sequencing identified a two-nucleotide deletion in OSBPL2 (c.158_159delAA) as the pathogenic variant for deafness in the family. Our finding expands the mutational spectrum of OSBPL2 and contributes to the pathogenic variant list in genetic counseling for deafness screening.

Clarification of glycosylphosphatidylinositol anchorage of OTOANCORIN and human OTOA variants associated with deafness.

Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remainpoorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G > C and p.Gln589ArgfsX55 [NM_144672.3]) .The pathogenic potential of c.1320 + 5 G > C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild-type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol-specific phospholipase C-induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI-anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI-anchorage.

Linkage of DFNB1 to non-syndromic neurosensory autosomal-recessive deafness in Mediterranean families.

Recent studies show a susceptibility locus (DFNB1) responsible for non-syndromic neurosensory autosomal-recessive deafness (NSRD) mapping to the pericentromeric region of chromosome 13q. In order to better understand the frequency with which DFNB1 is the gene for deafness in our patient population and the role of DFNB1 in Caucasians, we performed a genetic linkage study with four microsatellite markers linked to DFNB1 in a total of 48 independent Mediterranean families, of which 30 and 18 were of Italian and Spanish descent, respectively. A maximum two-point lod score of 7.28 was found with marker D13S115 at a recombination frequency of theta 0.1. Significant lod scores were also obtained for D13S143, D13S292 and D13S175. Genetic heterogeneity was confirmed using the HOMOG program which indicated absence of linkage to DFNB1 in approximately 21% of the sample. This study clearly demonstrates that DFNB1 plays an important role in 79% of Mediterranean families with NSRD. Furthermore, results from multipoint analysis predict that the DFNB1 gene maps between markers D13S175 and D13S115 which are separated by approximately 14.2 cM.

SLC26A4 pathogenic variants as a third cause of hearing loss: Role of three exons in DFNB4 deafness in Iran

Context: Pathogenic variants in SLC26A4 gene are the third-most frequent cause of autosomal recessive hearing loss in different populations. Aims: This article reports results of homozygosity mapping and SLC26A4 variant analysis in Iran. Settings and Design: A case series study was performed on forty GJB2-negative Iranian deaf families. Subjects and Methods: Homozygosity mapping, using microsatellite markers flanking the SLC26A4 gene, was performed on GJB2-negative Iranian deaf families. The SLC26A4 variant analysis was done by Sanger sequencing. A literature review was performed to identify all reported SLC26A4 pathogenic variants in Iran. Results: In one of the families, the hearing loss showed co-segregation with the DFNB4 STR markers. A previously reported SLC26A4 pathogenic variant was identified in homozygous state in all the affected members of this family. The literature review showed that variant screening of only three SLC26A4 exons and their boundary regions can detect variants responsible for deafness in about half of all DFNB4 Iranian deaf cases. Conclusions: The results of this study emphasize the important role of SLC26A4 pathogenic variants in the development of deafness in Iran. More information on the frequency of pathogenic variants can help in choosing faster and cost-effective methods for genetic testing.