New role of LRP5, associated with nonsyndromic autosomal-recessive hereditary hearing loss

Xia, Wenjun; Hu, Jiongjiong; Liu, Fei; Ma, Jing; Sun, Song; Zhang, Jin; Jin, Kaiyue; Huang, Jianbo; Jiang, Nan; Wang, Xu; Li, Wenwen; Ma, Zhiyuan; Ma, Duan

doi:10.1002/humu.23285

Cited by 10 publications

(8 citation statements)

References 44 publications

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“…Forty‐eight hours post‐fertilisation (hpf), transgenic zebrafish (Brn3C: EGFP) were anesthetised with MS222 (10 mg/mL), and then fixed with paraformaldehyde for 4 hours at room temperature. All the experimental procedures were performed as described previously . Rabbit anti‐sox2 antibody (GeneTex, Irvine, California) was used as the primary antibody, and 4′,6‐diamidino‐2‐phenylindole (DAPI) (1 mg/mL, Sigma‐Aldrich)‐stained cell nucleus and Alexa Fluor 594 Cy3 goat anti‐rabbit IgG (Jackson ImmunoResearch Laboratories, West Grove, Pennsylvania) were used as the secondary antibody.…”

Section: Whole‐exome Sequencingmentioning

confidence: 99%

“…The expression of trrap was detected using quantitative reverse transcription PCR (RT‐qPCR). The experimental procedures were performed as described previously . The cDNA products were amplified with the following PCR primers:…”

Section: Whole‐exome Sequencingmentioning

confidence: 99%

“…The experimental procedures were performed as described previously. 14 The cDNA products were amplified with the following PCR primers:…”

Section: Quantitative Reverse Transcription Pcrmentioning

confidence: 99%

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Novel TRRAP mutation causes autosomal dominant non‐syndromic hearing loss

Xia

et al. 2019

Clinical Genetics

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Hereditary non‐syndromic hearing loss is the most common inherited sensory defect in humans. More than 40 genes have been identified as causative genes for autosomal dominant non‐syndromic hearing loss (ADNSHL), but there are many other candidate genes that remain to be discovered. We aimed to identify the causative gene mutation for post‐lingual progressive ADNSHL in a Chinese family. Whole‐exome sequencing, bioinformatic analysis, and Sanger sequencing were used to verify the co‐segregation of a novel pathogenic variant (NM_ 001244580, c.511C>T, p.Arg171Cys) in the TRansformation/tRanscription domain‐Associated Protein gene associated with hearing loss in a three‐generation Chinese family with ADNSHL). Additionally, three more novel variants of transformation/transcription domain associated protein (TRRAP) were detected in 66 sporadic cases of hearing loss. Morpholino oligonucleotides knockdown and clustered regularly interspaced short palindromic repeats/Cas9 knockout zebrafish were constructed to validate the genetic findings. Knockdown or knockout of TRRAP resulted in significant defects in the inner ear of zebrafish, indicating that TRRAP plays an important role in inner ear development. In conclusion, TRRAP (NM_ 001244580, c.511C>T, p.Arg171Cys) co‐segregated with hearing loss in a Chinese family with ADNSHL, and TRRAP deficiency caused hearing disability in zebrafish, suggesting TRRAP is a gene associated with ADNSHL.

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Section: Whole‐exome Sequencingmentioning

confidence: 99%

Section: Whole‐exome Sequencingmentioning

confidence: 99%

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Novel TRRAP mutation causes autosomal dominant non‐syndromic hearing loss

Xia

et al. 2019

Clinical Genetics

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“…Cell proliferation assays were performed as described previously [8]. Proliferating cells were detected by targeting BrdU with mouse anti-BrdU IgG blocking serum (Santa Cruz Biotechnology, Dallas, TX, USA) and Alexa Fluor Ò 488-conjugated goat anti-mouse IgG (Jackson Immuno-Research Laboratories, West Grove, PA, USA) was used to detect BrdU antibody.…”

Section: Cell Proliferation Assaysmentioning

confidence: 99%

Mutations in TOP2B cause autosomal‐dominant hereditary hearing loss via inhibition of the PI3K‐Akt signalling pathway

Xia

et al. 2019

FEBS Letters

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Hereditary hearing impairment is a clinically and genetically heterogeneous disease. Whole‐exome sequencing was performed on seven affected and six unaffected members in a large Chinese family with autosomal‐dominant nonsyndromic hearing loss. The pathogenic variant of the gene encoding human topoisomerase IIβ TOP2B (c.G4837C:p.D1613H) was cosegregated with hearing loss in this pedigree and another two variants of TOP2B were detected in 66 sporadic patients with hearing loss. top2b knockdown led to significant defects in zebrafish inner ears and caused downregulation of akt which resulted in inactivation of PI3K‐Akt signalling. As a result, supporting cell and hair cell numbers were reduced through inhibition of the PI3K‐Akt pathway. Therefore, we hypothesized that mutations in TOP2B can cause autosomal‐dominant nonsyndromic hearing impairment through inhibition of the PI3K‐Akt signalling pathway. Database The whole‐exome sequence data in the study are available at the Sequence Read Archive database (NCBI) under the accession numbers , , , , , , , , , , . and , respectively.

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“…It has been estimated that ≥50% of cases of congenital deafness have genetic causes. At present, the etiology of hearing loss remains largely unknown, although gene alterations (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and environmental factors, including aminoglycoside antibiotics (AmAn), are now generally considered to be involved in this condition (16).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial tRNAIle A4317G mutation may be associated with hearing impairment in a Han Chinese family

Cui¹,

He²

2018

Mol Med Report

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Mutations in the mitochondrial genome have been identified to be associated with hearing loss. The aim of the present study was to investigate the role of mitochondrial DNA (mtDNA) variants in a Chinese family with hearing loss. Polymerase chain reaction (PCR)-Sanger sequencing was used to screen the mtDNA variants and nuclear genes [gap junction protein β2 (GJB2) and transfer (t)RNA 5-methylaminomethyle-2-thiouridylate methyltransferase (TRMU)]; in addition, the mtDNA copy number was determined by quantitative PCR. The present study characterized the molecular features of a Chinese family with maternally-inherited hearing loss and identified mtDNA A1555G and tRNA Ile A4317G mutations. The A4317G mutation was localized at the TΨC arm of tRNA Ile (position 59) and created a novel base-pairing (G59-C54), which may alter the secondary structure of the tRNA. In addition, patients carrying the A4317G mutation exhibited a lower mtDNA copy number compared with the controls, suggesting that this mutation may cause mitochondrial dysfunction that is responsible for the deafness. However, no functional variants in the GJB2 and TRMU genes were detected. mtDNA A1555G and A4317G mutations may contribute to the clinical manifestation of hearing loss in this family.

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New role of LRP5, associated with nonsyndromic autosomal-recessive hereditary hearing loss

Cited by 10 publications

References 44 publications

Novel TRRAP mutation causes autosomal dominant non‐syndromic hearing loss

Novel TRRAP mutation causes autosomal dominant non‐syndromic hearing loss

Mutations in TOP2B cause autosomal‐dominant hereditary hearing loss via inhibition of the PI3K‐Akt signalling pathway

Mitochondrial tRNAIle A4317G mutation may be associated with hearing impairment in a Han Chinese family

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