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Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome.


ABSTRACT: Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a Chinese family. Exome sequencing was used to identify the disease-causing gene for the two affected family members. Ophthalmic and physical examinations, as well as genetic screenings for variants in chimerin 1 (CHN1), were performed for all family members. Functional analyses of a CHN1 variant in 293T cells included a Rac-GTP activation assay, ?2-chimaerin translocation assay, and co-immunoprecipitation assay. Genetic analysis revealed a NM_001822.7: c.637T?>?G variant in the CHN1 gene, which resulted in the substitution of a highly conserved C1 domain with valine at codon 213 (NP_001813.1: p.(Phe213Val)) (ClinVar Accession Number: SCV001335305). In-silico analysis revealed that the p.(Phe213Val) substitution affected the protein stability and connections among the amino acids of CHN1 in terms of its tertiary protein structure. Functional studies indicated that the p.(Phe213Val) substitution reduced Rac-GTP activity and enhanced membrane translocation in response to phorbol-myristoyl acetate (PMA). Together with previous studies, our present findings demonstrate that CHN1 may be an important causative gene for different ethnicities with DRS.

SUBMITTER: Zhou TC 

PROVIDER: S-EPMC7531002 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Identification of a novel CHN1 p.(Phe213Val) variant in a large Han Chinese family with congenital Duane retraction syndrome.

Zhou Tai-Cheng TC   Duan Wen-Hua WH   Fu Xiao-Lin XL   Zhu Qin Q   Guo Li-Yun LY   Zhou Yuan Y   Hua Zhi-Juan ZJ   Li Xue-Jiao XJ   Yang Dong-Mei DM   Zhang Jie-Ying JY   Yin Jie J   Zhang Xiao-Fan XF   Zhou Guang-Long GL   Hu Min M  

Scientific reports 20201001 1


Duane retraction syndrome (DRS) is a neuromuscular dysfunction of the eyes. Although many causative genes of DRS have been identified in Europe and the United States, few reports have been published in regard to Chinese DRS. The aim of the present study was to explore the genetic defect of DRS in a Chinese family. Exome sequencing was used to identify the disease-causing gene for the two affected family members. Ophthalmic and physical examinations, as well as genetic screenings for variants in  ...[more]

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