Novel Variant in CEP250 Causes Protein Mislocalization and Leads to Nonsyndromic Autosomal Recessive Type of Progressive Hearing Loss

Kang, Minjin; Kim, Jung Ah; Song, Mee Hyun; Joo, Sun Young; Kim, Se Jin; Jang, Seung Hyun; Lee, Ho; Seong, Je Kyung; Choi, Jae Young; Gee, Heon Yung; Jung, Jinsei

doi:10.3390/cells12182328

Cited by 4 publications

(1 citation statement)

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“…CEP250, otherwise called C-NAP1, modulates centrosome cohesion, centriole biogenesis, and centrosome duplication at distinct cellular cycles ( 34 ). CEP family proteins critically maintain the checkpoint signal mechanism, along with centriole biogenesis.…”

Section: Discussionmentioning

confidence: 99%

Venous thromboembolism and severe COVID-19: a Mendelian randomization trial and transcriptomic analysis

Chen,

Dai

2024

Front. Immunol.

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IntroductionVenous thromboembolism (VTE) is known to be intricately linked to severe COVID-19 (sCOVID-19) occurrence. Herein, we employed univariable Mendelian randomization (MR) and transcriptome analysis to predict the causal association and associated signaling networks between VTE and sCOVID-19.MethodsPotential VTE and sCOVID-19 association was assessed using MR-Egger, weighted median, simple mode, weighted mode, and inverse variance weighted (IVW) regression. We conducted independent univariable analyses involving VTE and sCOVID-19. Using heterogeneity, pleiotropy, and the Leave-One-Out examinations, we performed sensitivity analyses. Thereafter, we performed transcriptome analysis of the GSE164805 dataset to identify differentially expressed genes (DEGs) linked to single nucleotide polymorphisms (SNPs). Lastly, we conducted immune analyses.ResultsBased on our univariable analysis, VTE was a strong indicator of sCOVID-19 development, and it was intricately linked to sCOVID-19. We further conducted sensitivity analysis to demonstrate the reliability of our results. Using differential analysis, we identified 15 major genes, namely, ACSS2, CEP250, CYP4V2, DDB2, EIF6, GBGT1, GSS, MADD, MAPK8IP1, MMP24, YBPC3, NT5DC3, PROCR, SURF6, and YIPF2, which were strongly connected to suppressive adaptive immune as well as augmented inflammatory cells. In addition, we uncovered strong associations with most differential immunologic gene sets, such as, the Major Histocompatibility Complex (MHC), immunoactivators, and immunosuppressors.ConclusionHerein, we demonstrated we strong association between VTE and enhanced sCOVID-19 risk. We also identified 15 DEGs which potentially contribute to the shared immunologic pathogenesis between VTE and sCOVID-19.

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Section: Discussionmentioning

confidence: 99%

Venous thromboembolism and severe COVID-19: a Mendelian randomization trial and transcriptomic analysis

Chen,

Dai

2024

Front. Immunol.

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Exploring the diverse clinical and variant spectrum of CEP78‐associated syndrome: Novel pathogenic variants identified in a case series

Zhai,

Ballios

2024

American J of Med Genetics Pt A

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Dual sensory impairment, commonly referred to as combined hearing and vision loss, can stem from a diverse spectrum of conditions, each presenting with its unique set of clinical characteristics. Our understanding of dual sensory impairment has expanded significantly in the past decade, broadening the scope of genetic differential diagnoses, including genes such as CEP250, ARSG, TUBB4B, CEP78, and ABHD12. A case series including three patients from two families with genetically diagnosed CEP78‐associated cone–rod dystrophy was identified. We collected and reviewed their clinical records, imaging data, and genetic testing results. In addition, a comprehensive literature review was conducted on the phenotype and the genetic testing modality employed in all published CEP78 cases through a PubMed search using the keyword “CEP78.” A retinal dystrophy panel detected a novel homozygous CEP78 pathogenic variant (c.1447C>T, p.Arg483*) in siblings—Cases 1 and 2—from Family 1. Both teenagers have a clinical diagnosis of cone–rod dystrophy with presumed normal hearing. Case 3 from Family 2, diagnosed with cone–rod dystrophy and early‐onset hearing loss, was found to carry a CEP78 pathogenic variant (c.1206‐2A>C) and a likely pathogenic variant (c.856_857del, p.Leu286Glyfs*12) also through panel‐based genetic testing. Intriguingly, neither of these variants was reported in an affected sibling's clinical whole‐exome sequencing (WES) report when performed in 2015. A review of CEP78‐related literature unveiled that the initial report linking CEP78 to cone–rod dystrophy and hearing loss was published in September 2016. Any pathogenic variant found in CEP78 before 2016 would have been categorized as a “clearly disruptive variant in a gene of uncertain significance (GUS)” and might not have been reported in the WES report. It is important to acknowledge that our understanding of genotype–phenotype associations is undergoing rapid expansion. It is also crucial to recognize that repeat genetic testing may represent a fundamentally different approach, given the technological advancements not only in the coverage of the sequencing but also in the more comprehensive understanding of genotype–phenotype associations. This case series also enriches the existing CEP78 literature by providing phenotypic details of the youngest case of CEP78‐associated retinopathy reported in the literature (Case 2), which expands our perspective on the natural history of disease in this disorder.

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AURKB and circAURKB_288aa enhance Esophageal cancer drug resistance through inducing abnormal centrosome separation

Lv,

Zhou,

Qiu

et al. 2025

Biochemical Pharmacology

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Novel Variant in CEP250 Causes Protein Mislocalization and Leads to Nonsyndromic Autosomal Recessive Type of Progressive Hearing Loss

Cited by 4 publications

References 35 publications

Venous thromboembolism and severe COVID-19: a Mendelian randomization trial and transcriptomic analysis

Venous thromboembolism and severe COVID-19: a Mendelian randomization trial and transcriptomic analysis

Exploring the diverse clinical and variant spectrum of CEP78‐associated syndrome: Novel pathogenic variants identified in a case series

AURKB and circAURKB_288aa enhance Esophageal cancer drug resistance through inducing abnormal centrosome separation

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