Hearing Loss in Baraitser-Winter Syndrome: Case Reports and Review of the Literature.

Background: Baraitser-Winter Syndrome (BRWS) is a rare autosomal dominant condition associated with hearing loss (HL). In the literature, two types of this condition are reported, Baraitser-Winter type 1 (BRWS1) and type 2 (BRWS2) produced by specific pathogenetic variants of two different genes, ACTB for BRWS1 and ACTG1 for BRWS2. In addition to syndromic BRWS2, some pathogenic variants in ACTG1 are associated also to another pathologic entity, the "Autosomal dominant non-syndromic hearing loss 20/26". In these syndromes, typical craniofacial features, sensory impairment (vision and hearing) and intellectual disabilities are frequently present. Heart anomalies, renal and gastrointestinal involvement and seizure are also common. Wide inter- and intra-familial variety in the phenotypic spectrum is reported. Some phenotypic aspects of these syndromes are not yet fully described, such as the degree and progression of HL, and better knowledge of them could be useful for correct follow-up and treatment. Methods and Results: In this study, we report two cases of children with HL and diagnosis of BRWS and a review of the current literature on HL in these syndromes.

MBD3 promotes epithelial-mesenchymal transition in gastric cancer cells by upregulating ACTG1 via the PI3K/AKT pathway.

BACKGROUND: Gastric cancer (GC) is a common malignancy and a leading cause of cancer-related death with high morbidity and mortality. Methyl-CpG binding domain protein 3 (MBD3), a key epigenetic regulator, is abnormally expressed in several cancers, participating in progression and metastasis. However, the role of MBD3 in GC remains unknown. METHODS: MBD3 expression was assessed via public databases and validated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The prognosis of MBD3 was analysed via bioinformatics based on the TCGA dataset. The migration, invasion and proliferation of GC cells were examined by transwell, wound healing, cell counting kit (CCK)-8, colony-formation and xenograft mouse models. Epithelial-mesenchymal transition (EMT) and phosphatidylinositide 3-kinases/ protein Kinase B (PI3K/AKT) pathway markers were evaluated by Western blotting. RNA sequencing was used to identify the target of MBD3. RESULTS: MBD3 expression was higher in GC tissues and cells than in normal tissues and cells. Additionally, high MBD3 levels were associated with poor prognosis in GC patients. Subsequently, we proved that MBD3 enhanced the migration, invasion and proliferation abilities of GC cells. Moreover, western blot results showed that MBD3 promoted EMT and activated the PI3K/AKT pathway. RNA sequencing analysis showed that MBD3 may increase actin γ1 (ACTG1) expression to promote migration and proliferation in GC cells. CONCLUSION: MBD3 promoted migration, invasion, proliferation and EMT by upregulating ACTG1 via PI3K/AKT signaling activation in GC cells and may be a potential diagnostic and prognostic target.

HMBA ameliorates obesity by MYH9- and ACTG1-dependent regulation of hypothalamic neuropeptides.

The global epidemic of obesity remains a daunting problem. Here, we report hexamethylene bisacetamide (HMBA) as a potent anti-obesity compound. Peripheral and central administration of HMBA to diet-induced obese mice regulated the expression of hypothalamic neuropeptides critical for energy balance, leading to beneficial metabolic effects such as anorexia and weight loss. We found that HMBA bound to MYH9 and ACTG1, which were required for the anti-obesity effects of HMBA in both NPY-expressing and POMC-expressing neurons. The binding of HMBA to MYH9 and ACTG1 elevated the expression of HEXIM1 and enhanced its interaction with MDM2, resulting in the dissociation of the HEXIM1-p53 complex in hypothalamic cells. Subsequently, the free HEXIM1 and p53 translocated to the nucleus, where they downregulated the transcription of orexigenic NPY, but p53 and acetylated histone 3 upregulated that of anorexigenic POMC. Our study points to a previously unappreciated efficacy of HMBA and reveals its mechanism of action in metabolic regulation, which may propose HMBA as a potential therapeutic strategy for obesity.

Bioinformatic identification and experiment validation revealed that ACTG1 is a promising prognostic signature and therapeutic target for sepsis.

In the intensive care unit, sepsis is a prevalent clinical syndrome (i.e. the final pathway to death from most infections). Peripheral blood gene expression profiling is becoming more and more accepted as a potential diagnostic or prognostic tool. This work aimed to recognize genes related to sepsis, providing potential translational therapeutic targets. RNA sequencing was performed on peripheral blood mononuclear cells from 20 healthy control subjects and 51 sepsis patients. Weighted gene coexpression network analysis was employed to pick out sepsis-related and immunocyte-related gene modules. Genes in the yellow module are primarily involved in excessive inflammation and immune suppression. STRING and Cytoscape were combined to identify ACTG1 and IQGAP1 as hub genes with highest connective degree, and prognostic predication value of ACTG1 was confirmed. Both univariate and multivariate logistic regression analyses were carried out. ACTG1 messenger RNA expression was increased in animal and in cell-related sepsis models. Small interfering RNA revealed decreasing ACTG1 can reduce the in vitro sepsis model apoptosis. We have authenticated ACTG1 as a reliable signature of a poor outcome of sepsis and promising therapeutic targets for sepsis.

A likely pathogenic ACTG1 variant in a child showing partial phenotypic overlap with Baraitser-Winter syndrome.

Baraitser-Winter syndrome (BRWS) is a rare autosomal dominant disease (AD) caused by heterozygous variants in ACTB (BRWS1) or ACTG1 (BRWS2) genes. BRWS features developmental delay/intellectual disability of variable degree and craniofacial dysmorphisms. Brain abnormalities (especially pachygyria), microcephaly, epilepsy, as well as hearing impairment, cardiovascular and genitourinary abnormalities may be present. We report on a 4-year-old female, who was addressed to our institution because of psychomotor delay associated with microcephaly and dysmorphic features, short stature, mild bilateral sensorineural hearing loss, mild cardiac septal hypertrophy, and abdominal swelling. Clinical exome sequencing detected a c.617G>A p.(Arg206Gln) de novo variant in ACTG1 gene. Such variant has been previously reported in association with a form of AD nonsyndromic sensorineural progressive hearing loss and we classified it as likely pathogenic according to ACMG/AMP criteria, despite our patient's phenotype only partially overlapped BWRS2. Our finding supports the extreme variability of the ACTG1-related disorders, ranging from classical BRWS2 to nuanced clinical expressions not fitting the original description, and occasionally featuring previously undescribed clinical findings.

Obsessive-compulsive symptoms in ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome.

Symptoms of obsessive-compulsive disorder (OCD) may rarely occur in the context of genetic syndromes. So far, an association between obsessive-compulsive symptoms (OCS) and ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome has not been described as yet. A thoroughly phenotyped patient with OCS and ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome is presented. The 25-year-old male patient was admitted to in-patient psychiatric care due to OCD. A whole-exome sequencing analysis was initiated as the patient also showed an autistic personality structure, below average intelligence measures, craniofacial dysmorphia signs, sensorineural hearing loss, and sinus cavernoma as well as subtle cardiac and ophthalmological alterations. The diagnosis of Baraitser-Winter cerebrofrontofacial syndrome type 2 was confirmed by the detection of a heterozygous likely pathogenic variant in the ACTG1 gene [c.1003C > T; p.(Arg335Cys), ACMG class 4]. The automated analysis of magnetic resonance imaging (MRI) revealed changes in the orbitofrontal, parietal, and occipital cortex of both sides and in the right mesiotemporal cortex. Electroencephalography (EEG) revealed intermittent rhythmic delta activity in the occipital and right temporal areas. Right mesiotemporal MRI and EEG alterations could be caused by a small brain parenchymal defect with hemosiderin deposits after a cavernomectomy. This paradigmatic case provides evidence of syndromic OCS in ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome. The MRI findings are compatible with a dysfunction of the cortico-striato-thalamo-cortical loops involved in OCD. If a common pathophysiology is confirmed in future studies, corresponding patients with Baraitser-Winter cerebrofrontofacial syndrome type 2 should be screened for OCS. The association may also contribute to a better understanding of OCD pathophysiology.

De Novo ACTG1 Variant Expands the Phenotype and Genotype of Partial Deafness and Baraitser-Winter Syndrome.

Actin molecules are fundamental for embryonic structural and functional differentiation; γ-actin is specifically required for the maintenance and function of cytoskeletal structures in the ear, resulting in hearing. Baraitser-Winter Syndrome (B-WS, OMIM #243310, #614583) is a rare, multiple-anomaly genetic disorder caused by mutations in either cytoplasmically expressed actin gene, ACTB (ß-actin) or ACTG1 (γ-actin). The resulting actinopathies cause characteristic cerebrofrontofacial and developmental traits, including progressive sensorineural deafness. Both ACTG1-related non-syndromic A20/A26 deafness and B-WS diagnoses are characterized by hypervariable penetrance in phenotype. Here, we identify a 28th patient worldwide carrying a mutated γ-actin ACTG1 allele, with mildly manifested cerebrofrontofacial B-WS traits, hypervariable penetrance of developmental traits and sensorineural hearing loss. This patient also displays brachycephaly and a complete absence of speech faculty, previously unreported for ACTG1-related B-WS or DFNA20/26 deafness, representing phenotypic expansion. The patient's exome sequence analyses (ES) confirms a de novo ACTG1 variant previously unlinked to the pathology. Additional microarray analysis uncover no further mutational basis for dual molecular diagnosis in our patient. We conclude that γ-actin c.542C > T, p.Ala181Val is a dominant pathogenic variant, associated with mildly manifested facial and cerebral traits typical of B-WS, hypervariable penetrance of developmental traits and sensorineural deafness. We further posit and present argument and evidence suggesting ACTG1-related non-syndromic DFNA20/A26 deafness is a manifestation of undiagnosed ACTG1-related B-WS.

Actin gamma 1 is a critical regulator of pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for about 90% of pancreatic cancers, which represents one of the most lethal malignancies with a 5-year overall survival less than 10%. Identifying molecular biomarkers is invaluable in helping to predict clinical outcomes and developing targeted chemotherapies. Actin gamma 1 (ACTG1) is a kind of actin isoform that exists in almost all cell types as a component of the cytoskeleton, thus mediating cell viability. Although there have been studies revealing the prognostic significance of ACTG1 in several malignancies such as glioblastoma and hepatocellular carcinoma, its involvement and function in pancreatic cancer needs to be elucidated. Methods: We retrospectively enrolled a cohort of PDAC patients after surgical resection (n = 149) and conducted immunohistochemistry experiments to explore the expression profile of ACTG1. Univariate and multivariate analyses were performed to investigate the clinical relevance of ACTG1. The functional role of ACTG1 in PDAC progression was further validated via both in vitro and in vivo studies. Results: ACTG1 presented a higher expression in PDAC tissues than in nontumorous pancreatic tissues. ACTG1 level positively correlated with tumor stage, implying its potential role as a tumor promoter. Univariate and multivariate analyses identified that patients with lower ACTG1 showed a better overall survival compared to those with higher ACTG1 expression. Cellular and xenograft experiments confirmed the role of ACTG1 on facilitating tumor proliferation both in vitro and in vivo. Conclusions: Our study revealed a pro-oncogenic role of ACTG1 in PDAC, which may help predict prognosis and serve as a novel therapeutic target.

Silencing ACTG1 Expression Induces Prostate Cancer Epithelial Mesenchymal Transition Through MAPK/ERK Signaling Pathway.

Purpose: Metastatic prostate cancer (PCa) has become a major obstacle in the treatment of PCa. The study's purpose is to find biomarkers of tumor metastasis by proteomics and enzyme-linked immunosorbent assay (ELISA), and to design related experiments to study its role in the progress and metastasis of PCa. Method: We analyzed serum from primary PCa stage and metastatic stage of 12 patients to find metastatic PCa serum protein biomarkers using isobaric tags for relative and absolute quantitation (iTRAQ). An effective diagnostic model based on validated biomarkers using logistic regression was established. In vivo and in vitro biological behavior experiments (wound healing, CCK8, and Transwell tests) were carried out after obtaining the biomarkers. Related mechanism has been studied, which may be associated with metastatic PCa. Result: Actin gamma 1 (ACTG1) is a potential biomarker in the metastasis of PCa. Bioinformatics and related experiments show that ACTG1 is high-expressed in PCa tissues and cells. In vivo and in vitro experiments illustrated that the ability of proliferation, migration, and invasion of PCa cells was significantly inhibited after the knockdown of ACTG1 expression. Surprisingly, ERK protein expression was downregulated after ACTG1 knockdown. At the same time, the expression of epithelial-mesenchymal transition-related markers in PCa cells decrease after treated with ERK1/2 inhibitor, which indicating that ACTG1 may affect the metastatic ability of PCa cells through MAPK/ERK signaling pathway. Conclusion: ACTG1 is a marker of metastasis PCa. It mediates cell proliferation and may regulate the metastasis of PCa through MAPK/ERK signaling pathway, which provides a useful theoretical basis for exploring the treatment of PCa.

DFNA20/26 and Other ACTG1-Associated Phenotypes: A Case Report and Review of the Literature.

Since the early 2000s, an ever-increasing subset of missense pathogenic variants in the ACTG1 gene has been associated with an autosomal-dominant, progressive, typically post-lingual non-syndromic hearing loss (NSHL) condition designed as DFNA20/26. ACTG1 gene encodes gamma actin, the predominant actin protein in the cytoskeleton of auditory hair cells; its normal expression and function are essential for the stereocilia maintenance. Different gain-of-function pathogenic variants of ACTG1 have been associated with two major phenotypes: DFNA20/26 and Baraitser-Winter syndrome, a multiple congenital anomaly disorder. Here, we report a novel ACTG1 variant [c.625G>A (p. Val209Met)] in an adult patient with moderate-severe NSHL characterized by a downsloping audiogram. The patient, who had a clinical history of slowly progressive NSHL and tinnitus, was referred to our laboratory for the analysis of a large panel of NSHL-associated genes by next generation sequencing. An extensive review of previously reported ACTG1 variants and their associated phenotypes was also performed.

When Familial Hearing Loss Means Genetic Heterogeneity: A Model Case Report.

We describe a family with both hearing loss (HL) and thrombocytopenia, caused by pathogenic variants in three genes. The proband was a child with neonatal thrombocytopenia, childhood-onset HL, hyper-laxity and severe myopia. The child's mother (and some of her relatives) presented with moderate thrombocytopenia and adulthood-onset HL. The child's father (and some of his relatives) presented with adult-onset HL. An HL panel analysis, completed by whole exome sequencing, was performed in this complex family. We identified three pathogenic variants in three different genes: MYH9, MYO7A and ACTG1. The thrombocytopenia in the child and her mother is explained by the MYH9 variant. The post-lingual HL in the paternal branch is explained by the MYO7A variant, absent in the proband, while the congenital HL of the child is explained by a de novo ACTG1 variant. This family, in which HL segregates, illustrates that multiple genetic conditions coexist in individuals and make patient care more complex than expected.

ACTG1 regulates intervertebral disc degeneration via the NF-κB-p65 and Akt pathways.

ACTG1 is a member of the actin family but is not a muscle actin gene. The ACTG1 mutation leads to hearing loss in humans, and the knockdown of ACTG1 suppresses the proliferation and migration of tumor cells; however, its role in intervertebral disc degeneration (IDD) is yet unclear. Bioinformatics methods revealed that ACTG1 might be a hub gene in IDD. Furthermore, the expression ACTG1 in severely degenerated nucleus pulposus (NP) tissues (Pfirrmann grade IV and V) was low as compared to that in mildly degenerated samples (Pfirrmann grade II and III). Moreover, the ACTG1 level was negatively correlated with human disc degeneration grades. The low expression of ACTG1 is also found in degenerated NP tissues in the rat. To further explore the function of ACTG1 in IDD, the gene expression was depleted in human NP cells via siRNA transfection. The ablation of ACTG1 increased MMP3 expression but decreased the level of collagen II. Excessive apoptosis was observed in ACTG1 knockdown groups, indicating that the absence of ACTG1 exacerbated IDD. GO function and pathway enrichment analysis for differentially expressed genes (DEGs) of two microarray datasets (GSE56081 and GSE42611) indicated that inflammatory response plays a crucial role in IDD. Interestingly, in the protein-protein interaction (PPI) network, ACTG1 is connected to the proteins of inflammation-related pathways. Furthermore, ACTG1 knockdown upregulated P-P65 level but suppressed P-Akt expression. These data collectively demonstrated that ACTG1 regulated the development of IDD through the NF-κB-p65 and Akt pathways, and ACTG1 may be a novel marker and therapeutic target of IDD in the future.

Genomic Amplification and Functional Dependency of the Gamma Actin Gene ACTG1 in Uterine Cancer.

Sarcomere and cytoskeleton genes, or actomyosin genes, regulate cell biology including mechanical stress, cell motility, and cell division. While actomyosin genes are recurrently dysregulated in cancers, their oncogenic roles have not been examined in a lineage-specific fashion. In this report, we investigated dysregulation of nine sarcomeric and cytoskeletal genes across 20 cancer lineages. We found that uterine cancers harbored the highest frequencies of amplification and overexpression of the gamma actin gene, ACTG1. Each of the four subtypes of uterine cancers, mixed endometrial carcinomas, serous carcinomas, endometroid carcinomas, and carcinosarcomas harbored between 5~20% of ACTG1 gene amplification or overexpression. Clinically, patients with ACTG1 gains had a poor prognosis. ACTG1 gains showed transcriptional patterns that reflect activation of oncogenic signals, repressed response to innate immunity, or immunotherapy. Functionally, the CRISPR-CAS9 gene deletion of ACTG1 had the most robust and consistent effects in uterine cancer cells relative to 20 other lineages. Overall, we propose that ACTG1 regulates the fitness of uterine cancer cells by modulating cell-intrinsic properties and the tumor microenvironment. In summary, the ACTG1 functions relative to other actomyosin genes support the notion that it is a potential biomarker and a target gene in uterine cancer precision therapies.

COX10-AS1 Facilitates Cell Proliferation and Inhibits Cell Apoptosis in Glioblastoma Cells at Post-Transcription Level.

Glioblastoma (GBM) is an invasive cancer with poor prognosis in patients. Researching on molecular functions in GBM has attracted more and more attention. Actin gamma 1 (ACTG1) was reported as a pathogenic gene in skin cancer and colorectal cancer. Present study was designed to explore the biological role and underlying mechanism of ACTG1 in GBM cells. It was uncovered that ACTG1 presented high expression trends in GBM cells. Moreover, ACTG1 suppression hindered cell proliferation and boosted cell apoptosis in GBM. Then, according to the results of bioinformatics analysis and mechanism assays including RIP, RNA pull down and luciferase reporter assay, ACTG1 was verified to be targeted by miR-361-5p in GBM. Next, COX10-AS1 (COX10 antisense RNA 1) was identified as an endogenous sponge for miR-361-5p in GBM. Moreover, COX10-AS1 acted as a competing endogenous RNA (ceRNA) to positively regulate ACTG1 expression via sponging miR-361-5p. The following rescue assays demonstrated that COX10-AS1 promoted GBM cell proliferation and inhibited GBM cell apoptosis through ACTG1 up-regulation at a miR-361-5p dependent way. On the whole, present study uncovered a novel ceRNA pattern in which COX10-AS1 sponged miR-361-5p to elevate ACTG1 expression, therefore accelerating tumorigenesis in GBM. The findings suggested new promising targets for GBM treatment.

Baraitser-Winter cerebrofrontofacial syndrome: Report of two adult siblings.

Baraitser-Winter cerebrofrontofacial syndrome (BWCS) is a rare, autosomal dominant condition that is characterized by intellectual disability, distinctive craniofacial features, structural brain abnormalities, seizures, microcephaly, hearing loss, and ocular colobomas. The first three cases were described in 1988 by Baraitser and Winter and included two siblings and an unrelated third patient. Subsequently, causative missense variants in the ACTB and ACTG1 genes were identified, with de novo occurrence in patients with the condition. Herein, we describe two adult siblings who were born to unaffected parents and who were diagnosed with BWCS in their fourth and sixth decade of life following exome sequencing performed for intellectual disability. We review the literature reports of adult patients with BWCS to document the clinical features and phenotypic variability that can occur later in life. This is the first molecularly confirmed report of germline mosaicism in BWCS and one of only a few reports to describe two BWCS patients belonging to the same family.

Regulation of Actg1 and Gsta2 is possible mechanism by which capsaicin alleviates apoptosis in cell model of 6-OHDA-induced Parkinson's disease.

The present study aimed to identify the gene expression changes conferred by capsaicin in the cell model of 6-OHDA-induced Parkinson's disease, to disclose the molecular mechanism of action of capsaicin. We used capsaicin-treated and paraffin-embedded wax blocks containing substantia nigra tissue from 6-OHDA-induced Parkinson's disease rats to analyze transcriptional changes using Affymetrix GeneChip Whole Transcript Expression Arrays. A total of 108 genes were differentially expressed in response to capsaicin treatment, and seven of these genes were selected for further analysis: Olr724, COX1, Gsta2, Rab5a, Potef, Actg1, and Acadsb, of which Actg1 (actin gamma 1) was down-regulated and Gsta2 (Glutathione S-transferase alpha 2) was up-regulated. We successfully overexpressed Actg1 and Gsta2 in vitro. CCK-8 detection and flow cytometry demonstrated that overexpression of Actg1 and Gsta2 increased apoptosis in the 6-OHDA-induced Parkinson's disease cell model. The imbalance between Actg1 and Gsta2 may be one of the mechanisms of cell damage in Parkinson's disease (PD). Capsaicin can protect the cells and reduce the apoptosis rate by regulating Actg1 and Gsta2.

Prevalence of Cytoplasmic Actin Mutations in Diffuse Large B-Cell Lymphoma and Multiple Myeloma: A Functional Assessment Based on Actin Three-Dimensional Structures.

Mutations in actins have been linked to several developmental diseases. Their occurrence across different cancers has, however, not been investigated. Using the cBioPortal database we show that human actins are infrequently mutated in patient samples of various cancers types. Nevertheless, ranking these studies by mutational frequency suggest that some have a higher percentage of patients with ACTB and ACTG1 mutations. Within studies on hematological cancers, mutations in ACTB and ACTG1 are associated with lymphoid cancers since none have currently been reported in myeloid cancers. Within the different types of lymphoid cancers ACTB mutations are most frequent in diffuse large B-cell lymphoma (DLBCL) and ACTG1 mutations in multiple myeloma. We mapped the ACTB and ACTG1 mutations found in these two cancer types on the 3D-structure of actin showing they are in regions important for actin polymer formation or binding to myosin. The potential effects of the mutations on actin properties imply that mutations in cytoplasmic actins deserve dedicated research in DLBCL and multiple myeloma.

Previously undescribed phenotypic findings and novel ACTG1 gene pathogenic variants in Baraitser-Winter cerebrofrontofacial syndrome.

Baraitser-Winter cerebrofrontofacial syndrome is an autosomal dominant disease characterized by multiple congenital abnormalities and intellectual disability, which is caused by mutations in either the ACTB or ACTG1 genes. In this report, we described novel phenotypic findings in two Mexican patients with the disorder in whom two novel ACTG1 mutations (c.176A > G, p.Gln59Arg; and c.608C > T, p.Thr203Met) were identified.

Amino acid 118 in the Deafness Causing (DFNA20/26) ACTG1 gene is a Mutational Hot Spot.

BACKGROUND: Hearing loss is an economically and socially important cause of human morbidity, affecting 360 million people (over 5% of the world's population), of whom 32 million are children. Of the estimated minimum of 50% of hereditary hearing loss, non-syndromic hearing loss (NSHL) accounts for more than 70%. The autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous. To date, 67 ADNSHL loci (DFNA1-67) have been mapped; however, only 35 causative genes have been cloned since 1997 (http://hereditaryhearingloss.org/). METHODS: To identify the genetic basis of hereditary hearing loss in a Chinese family with ADNSHL, we undertook a targeted sequencing of 180 genes using a custom capture panel (MiamiOtoGenes). RESULTS: The onset of hearing loss in the family occurred between the ages of 15 and 18 years. Hearing loss was bilateral, started in the high frequency and progressed to lower frequencies. The c.353A>T (K118M) in the AC TG1 gene was identified by panel and was confirmed by Sanger sequencing and was present in all affected family members. So far, five of the 23 DFNA20/26 families worldwide have been found to carry mutation involving the residue K118. CONCLUSIONS: This is the first report of K118M mutation in the ACTG1 gene causing hearing loss in the Chinese population. The present data are in line with previous evidence to suggest that codon K118 of ACTG1 may represent a mutational hot spot that justifies a mutation screen for diagnostic purpose in the genetically heterogeneous group of DFNA20/26.

Outcomes of cochlear implantation for the patients with specific genetic etiologies: a systematic literature review.

CONCLUSION: Most of the cases with gene mutations of intra-cochlear etiology showed relatively good CI outcomes. To progress toward more solid evidence-based CI intervention, a greater number of reports including CI outcomes for specific gene mutations are desired. BACKGROUND: Cochlear implantation (CI) is the most important and effective treatment for patients with profound sensorineural hearing loss. However, the outcomes of CI vary among patients. One of the reasons of this heterogeneous outcome for cochlear implantation is thought to be the heterogeneous nature of hearing loss. Indeed, genetic factors, the most common etiology in severe-to-profound hearing loss, might be one of the key determinants of outcomes for CI and electric acoustic stimulation (EAS). Patients with genetic causes involving an 'intra-cochlear' etiology show good CI/EAS outcomes. REVIEW: This review article aimed to summarize the reports on CI/EAS outcomes in patients with special genetic causes as well as to assist in future clinical decision-making. Most of the cases were suspected of an intra-cochlear etiology, such as those with GJB2, SLC26A4, and OTOF mutations, which showed relatively good CI outcomes. However, there have only been a limited number of reports on patients with other gene mutations.