PUBLICATION

Two novel CHN1 variants identified in Duane retraction syndrome pedigrees disrupt development of ocular motor nerves in zebrafish

Authors
Zhang, R., Jia, H., Chang, Q., Zhang, Z., Peng, C., Ma, Q., Liang, Y., Yang, S., Jiao, Y.
ID
ZDB-PUB-231019-59
Date
2023
Source
Journal of Human Genetics   69(1): 33-39 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Duane Retraction Syndrome*/genetics
  • Eye Abnormalities*
  • Humans
  • Mutation, Missense
  • Pedigree
  • Zebrafish/genetics
(all 7)
PubMed
37853116 Full text @ J. Hum. Genet.
Abstract
Duane retraction syndrome (DRS) is a rare congenital eye movement disorder causing by the dysplasia of abducens nerve, and has highly variable phenotype. MRI can reveal the endophenotype of DRS. Most DRS cases are sporadical and isolated, while some are familial or accompanied by other ocular disorders and systemic congenital abnormalities. CHN1 was the most common causative gene for familial DRS. Until now, 13 missense variants of CHN1 have been reported. In this study, we enrolled two unrelated pedigrees with DRS. Detailed clinical examinations, MRI, and the whole exome sequencing (WES) were performed to reveal their clinical and genetic characteristics. Patients from pedigree-1 presented with isolated DRS, and a novel heterozygous variant c.650 A > G, p. His217Arg was identified in CHN1 gene. Patients from pedigree-2 presented with classic DRS and abnormalities in auricle morphology, and the pedigree segregated another novel heterozygous CHN1 variant c.637 T > C, p. Phe213Leu. A variety of bioinformatics software predicted that the two variants had deleterious or disease-causing effects. After injecting of two mutant CHN1 mRNAs into zebrafish embryos, the dysplasia of ocular motor nerves (OMN) was observed. Our present findings expanded the phenotypic and genotypic spectrum of CHN1 related DRS, as well as provided new insights into the role of CHN1 in OMN development. Genetic testing is strongly recommended for patients with a DRS family history or accompanying systemic congenital abnormalities.
Genes / Markers
Marker Marker Type Name
chn1GENEchimerin 1
1 - 1 of 1
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Figures
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Expression
No data available
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
rw0TgTransgenic Insertion
    vu19TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      1 - 1 of 1
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      Sequence Targeting Reagents
      Target Reagent Reagent Type
      chn1MO1-chn1MRPHLNO
      1 - 1 of 1
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      Fish
      1 - 1 of 1
      Show
      Antibodies
      Orthology
      Engineered Foreign Genes
      Marker Marker Type Name
      DsRed2EFGDsRed2
      GFPEFGGFP
      1 - 2 of 2
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      Mapping