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  2. Whole-exome sequencing identified novel variants in CPLANE1 that causes oral-facial-digital syndrome Ⅵ by inducing primary cilia abnormality

Whole-exome sequencing identified novel variants in CPLANE1 that causes oral-facial-digital syndrome Ⅵ by inducing primary cilia abnormality

  • J Cell Mol Med. 2022 Jun;26(11):3213-3222. doi: 10.1111/jcmm.17326.
Wen Qian 1 Xinlei Liu 1 Zhengrong Wang 1 2 Yongjie Xu 3 Jingzhi Zhang 3 Haizhi Li 4 Qiang Zhong 4 Chengcheng Li 1 Liying Zhu 2 Zunlun Zhou 4 Wei Pan 1 2 3
Affiliations

Affiliations

  • 1 Prenatal Diagnosis Center in Guizhou Province, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
  • 2 School of Medical Laboratory, Guizhou Medical University, Guiyang, China.
  • 3 School of Public Health, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Guizhou Medical University, Guiyang, China.
  • 4 Department of Obstetrics and Gynecology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Abstract

Oral-facial-digital syndrome (OFDS) is a multisystemic ciliopathic disorder with an autosomal recessive mode of inheritance. OFDS usually manifests with typical craniofacial anomalies and variable occurrence of polydactyly. Germline variants in CPLANE1 cause OFDS VI. In this study, we investigated a 26-year-old Chinese female patient who was 23+1 weeks pregnant. She had a history of adverse pregnancy outcomes with multiple foetal malformations. We performed ultrasonography and identified the foetus as having a posterior fossa Blake cyst and postaxial polydactyly. The patient decided to terminate her pregnancy, and further genetic molecular analysis was performed. We identified the aborted foetus as having postaxial polydactyly. Whole-exome Sequencing identified a missense variant (c.3599C>T, p.A1200V) in exon 20 and a c.834+1G>T variant in exon 7 of CPLANE1 (NM_023073.3) in the foetus. Sanger Sequencing confirmed that these variants came from the parents of the foetus. In this study, we investigated a family with OFDS VI through genetic testing and bioinformatics analysis, which provided powerful help for prenatal diagnosis. Then, we demonstrated that the cell migration rate and the number of cilia were decreased after interference with CPLANE1 expression in NIH/3T3 cells. After CPLANE1 knockdown, the Hh signalling pathway was inhibited, and the Hh pathway activator SAG reversed the inhibitory effect. This is the first report of a family with OFDS VI in the Chinese population.

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