Novel compound heterozygous synonymous and missense variants in the <i>MYO7A</i> gene identified by next‐generation sequencing in a Chinese family with nonsyndromic hearing loss

Xiang, Yanbao; Xu, Chenyang; Xu, Yuesheng; Zhou, Lili; Tang, Shaohua; Xu, Xueqin

doi:10.1002/jcla.24708

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…MYO7A, a member of the unconventional myosin family, encodes the protein myosin VIIA 59 . MYO7A is primarily expressed in the cochlear and vestibular neuroepithelia of the inner ear, 60 the retinal pigment epithelium, and photoreceptors 61 . Mutations in MYO7A have been reported to cause mitochondrial damage and dysfunction 62 .…”

Section: Discussionmentioning

confidence: 99%

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population

Wu,

Zhang,

Duan

et al. 2024

Diabetes Obesity Metabolism

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AimThe liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non‐alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed use systematic investigation of the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus.Materials and methodsOral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high‐fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi‐criteria approach and in vitro validated to confirm their functional relevance.ResultsOur results showed that plasma glucose levels in the oral glucose tolerance test were significantly affected by both diet and genetic background. To identify further the candidate genes associated with hepatic glucose metabolism, the results revealed nine genetic regulating loci on chromosomes 1, 4, 7 and 11, respectively, by quantitative trait loci mapping. Moreover, TEA Domain Transcription Factor 1 (TEAD1), myosin VIIA (MYO7A) and NADH:ubiquinone oxidoreductase subunit C2 (NDUFC2) were identified as the candidate functional genes. Functionally, siRNA‐mediated TEAD1, MYO7A and NDUFC2 significantly decreased glucose uptake. Reverse transcription‐polymerase chain reaction assays confirmed that the downregulation of those three candidates inhibited the transcription of genes related to insulin and glucose metabolism pathways.ConclusionsOur study contributes novel insights to the understanding of hepatic glucose metabolish, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.

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Section: Discussionmentioning

confidence: 99%

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population

Wu,

Zhang,

Duan

et al. 2024

Diabetes Obesity Metabolism

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Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next‐generation sequencing in a Chinese family with nonsyndromic hearing loss

Xiang

et al. 2022

Clinical Laboratory Analysis

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Background Variants in the MYO7A gene are increasingly identified among patients suffering from Usher syndrome type 1B (USH1B). However, such mutations are less commonly detected among patients suffering from nonsyndromic hearing loss (NSHL), including autosomal recessive deafness (DFNB2) and autosomal dominant deafness (DFNA11). This research attempts to clarify the genetic base of DFNB2 in a Chinese family and determine the pathogenicity of the identified mutations. Method Targeted next‐generation sequencing (TGS) of 127 known deafness genes was performed for the 14‐year‐old proband. Then, Sanger sequencing was performed on the available family members. A minigene splicing assay was performed to verify the impact of the novel MYO7A synonymous variant. After performing targeted next‐generation sequencing (TGS) of 127 existing hearing loss‐related genes in a 14‐year‐old proband, Sanger sequencing was carried out on the available family members. Then, to confirm the influence of the novel MYO7A synonymous variants, a minigene splicing assay was performed. Results Two heteroallelic mutants of MYO7A (NM_000260.3) were identified: a maternally inherited synonymous variant c.2904G > A (p.Glu968=) in exon 23 and a paternally inherited missense variant c.5994G > T (p.Trp1998Cys) in exon 44. The in vitro minigene expression indicated that c.2904G > A may result in skipping of exon 23 resulting in a truncated protein. Conclusions We reported a novel missense (c.5994G > T) and identified, for the first time, a novel pathogenic synonymous (c.2904G > A) variant within MYO7A in a patient with DFNB2. These findings enrich our understanding of the MYO7A variant spectrum of DFNB2 and can contribute to accurate genetic counseling and diagnosis of NSHL patients.

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TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population

Chi,

Wu,

Zhang

et al. 2023

Preprint

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The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause Non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidemia, etc. Systematic investigation of the key factors related to hepatic glucose metabolism may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. Here, we quantified oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes in BXD mice under chow and high-fat diet conditions. Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background. To further identify the candidate genes associated with hepatic glucose metabolism, and the results revealed 9 genetic regulating loci on chromosomes 1, 4, 7 and 11, respectively by QTL mapping. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate functional genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 significantly decreased the glucose uptake. RT-PCR assays confirmed that the down-regulation of those three candidates inhibited the transcription of genes related to insulin and glucose metabolism pathways. Consequently, our study uncovered the role of TEAD1, MYO7A and NDUFC2 that influenced the mitochondrial function in to regulate glucose homeostasis and provided novel targets for the diagnosis, treatment, and prognosis of glucose metabolism-related diseases.

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Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next‐generation sequencing in a Chinese family with nonsyndromic hearing loss

Cited by 3 publications

References 39 publications

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population

Novel compound heterozygous synonymous and missense variants in the MYO7A gene identified by next‐generation sequencing in a Chinese family with nonsyndromic hearing loss

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population

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