Similar Datasets
Project description:The GJB6 gene is located just 35 kb telomeric to GJB2 in the so-called nonsyndromic hearing loss and deafness locus 1 (DFNB1). Knock out mouse models confirmed that inner ear expression of their protein products, connexin 30 (Cx30) and connexin 26 (Cx26), is crucial for hearing acquisition and normal development of the organ of Corti, however the coordinated regulation mechanism of Cx26 and Cx30 expression in the cochlea remains unclear. To investigate the mechanism underlying the etiopathogenesis of DFNB1, we used a microRNA (miRNA) and mRNA integrated expression profiling analysis on Cx30 -/- mice, which represent a model for humans in which large deletions in the DFNB1 locus lead to the down-regulation of both connexins and profound deafness.
2020-12-29 | GSE151367 | GEO
Project description:The GJB6 gene is located just 35 kb telomeric to GJB2 in the so-called nonsyndromic hearing loss and deafness locus 1 (DFNB1). Knock out mouse models confirmed that inner ear expression of their protein products, connexin 30 (Cx30) and connexin 26 (Cx26), is crucial for hearing acquisition and normal development of the organ of Corti, however the coordinated regulation mechanism of Cx26 and Cx30 expression in the cochlea remains unclear. To investigate the mechanism underlying the etiopathogenesis of DFNB1, we used a microRNA (miRNA) and mRNA integrated expression profiling analysis on Cx30 -/- mice, which represent a model for humans in which large deletions in the DFNB1 locus lead to the down-regulation of both connexins and profound deafness.
2020-12-29 | GSE151368 | GEO
Project description:The genetics of both syndromic (SHL) and non-syndromic hearing loss (NSHL) is characterized by a high degree of genetic heterogeneity. We analyzed whole exome sequencing data of 102 unrelated probands with apparently NSHL without a causative variant in known NSHL genes. We detected five causative variants in different SHL genes (SOX10, MITF, PTPN11, CHD7, and KMT2D) in five (4.9%) probands. Clinical re-evaluation of these probands shows that some of them have subtle syndromic findings, while none of them meets clinical criteria for the diagnosis of the associated syndrome (Waardenburg (SOX10 and MITF), Kallmann (CHD7 and SOX10), Noonan/LEOPARD (PTPN11), CHARGE (CHD7), or Kabuki (KMT2D). This study demonstrates that individuals who are evaluated for NSHL can have pathogenic variants in SHL genes that are not usually considered for etiologic studies.
| S-EPMC4999867 | biostudies-literature
Project description:MicroRNA and mRNA integrated transcriptional analysis in a Cx30-/- mouse model of non-syndromic hearing loss and deafness [mRNA]
| PRJNA635630 | ENA
Project description:MicroRNA and mRNA integrated transcriptional analysis in a Cx30-/- mouse model of non-syndromic hearing loss and deafness
| PRJNA635624 | ENA
Project description:MicroRNA and mRNA integrated transcriptional analysis in a Cx30-/- mouse model of non-syndromic hearing loss and deafness [miRNA]
| PRJNA635631 | ENA
Project description:BackgroundHearing impairment is one of most frequent birth defects, which affects nearly 1 in every 1,000 live births. However, the molecular etiology of non-syndromic deafness in China is not well studied. Here, we have investigated the presence of mutations in three genes commonly mutated in non-syndromic deafness patients in Shanxi Province, which has the highest frequency of birth defects in China.MethodsIn total, 1,201 unrelated non-syndromic deafness patients and 300 healthy individuals were enrolled. The hearing ability was confirmed by audiologic evaluation. Three major deafness-related genes (GJB2, SLC26A4 (PDS), and mtDNA 12S rRNA) of all individuals enrolled were analyzed by Sanger sequencing.ResultsThe results showed that GJB2 mutations accounted for 21.23% (255/1,201) in the patient group, with c.235delC, a hotspot mutation, accounting for 10.99% (132/1,201). Moreover, 11 new GJB2 mutations were identified. SLC26A4 mutations accounted for 9.33% (112/1,201) in the patient group, with IVS7-2A>G as the most prevalent mutation accounting for 4.75% (57/1,201). In addition, 15 patients (1.25%) were found to carry mtDNA 12S rRNA c.1555A>G mutation, while only two cases had the mtDNA 12S rRNA c.1494C>T.ConclusionIn our research, it was found that c.235delC in GJB2 and c.919-2A>G (IVS7-2A>G) in SLC26A4 were the highest frequency pathogenic variants in Shanxi Province. Taken together, our data will enrich the database of deafness mutations and will help clinical diagnosis, treatment, and genetic counseling of hearing impairment.
| S-EPMC6418354 | biostudies-literature
Project description:Mutations of the human ATP6V1B1 gene cause distal renal tubular acidosis (dRTA; OMIM #267300) often associated with sensorineural hearing impairment; however, mice with a knockout mutation of Atp6v1b1 were reported to exhibit a compensated acidosis and normal hearing. We discovered a new spontaneous mutation (vortex, symbol vtx) of Atp6v1b1 in an MRL/MpJ (MRL) colony of mice. In contrast to the reported phenotype of the knockout mouse, which was developed on a primarily C57BL/6 (B6) strain background, MRL-Atp6v1b1vtx/vtx mutant mice exhibit profound hearing impairment, which is associated with enlarged endolymphatic compartments of the inner ear. Mutant mice have alkaline urine but do not exhibit overt metabolic acidosis, a renal phenotype similar to that of the Atpbv1b1 knockout mouse. The abnormal inner ear phenotype of MRL- Atp6v1b1vtx/vtx mice was lost when the mutation was transferred onto the C57BL/6J (B6) background, indicating the influence of strain-specific genetic modifiers. To genetically map modifier loci in Atp6v1b1vtx/vtx mice, we analysed ABR thresholds of progeny from a backcross segregating MRL and B6 alleles. We found statistically significant linkage with a locus on Chr 13 that accounts for about 20% of the hearing threshold variation in the backcross mice. The important effect that genetic background has on the inner ear phenotype of Atp6v1b1 mutant mice provides insight into the hearing loss variability associated with dRTA caused by ATP6V1B1 mutations. Because MRL-Atp6v1b1vxt/vtx mice do not recapitulate the metabolic acidosis of dRTA patients, they provide a new genetic model for nonsyndromic deafness with enlarged vestibular aqueduct (EVA; OMIM #600791).
| S-EPMC5886195 | biostudies-literature
Project description:The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4%). Overall, seven missense variants (53.8%), three nonsense variants (23.1%), two frameshift variants (15.4%), and one splice-site variant (7.7%) were observed. Syndromic HL was identified in five (23.8%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.
| S-EPMC7709052 | biostudies-literature
Project description:Conventionally the etiology of congenital Non-Syndromic Hearing Loss has been attributed to mutations in the genes involved in ion homeostasis or the structural compartments of the inner ear. However, this contributes to only a part of the problem, as still the determinants for a large majority of the Non-Syndromic Hearing loss seems to be an enigma. Evidences indicate that pathogens like Rubella, Cytomegalovirus, and many other infections can also result in congenital hearing loss. Additionally, there are variety of factors other than the viral mediators, that can act as stressors to trigger an altered immune response, during the gestational period of the mother. It is also known that non-specific stimulation of the immune system can mimic an infection status. This indicates a strong role for environmental factors toward their contribution to the pathology, possibly by influencing the host immune response. These varieties of known or unknown environmental factors interact with the susceptible variants in immune response genes in defining the threshold for protection or infection in an individual. Considering this background we propose to present this perspective that threshold of the host immune response during the prenatal conditions, in response to environmental stimulus, might be determined by the susceptible variants in immune response genes. This in turn can directly or indirectly influence the genes involved in maintaining the structural components or ion homeostasis, resulting in hearing loss. The threshold of immune response alterations may be heavily dependent on the immunogenetic profile of the mother or the fetus.
| S-EPMC6919260 | biostudies-literature