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A novel FOXL2 mutation in two infertile patients with blepharophimosis–ptosis–epicanthus inversus syndrome

  • Genetics
  • Published:
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Abstract

Background

Blepharophimosis–ptosis–epicanthus inversus syndrome (BPES) is a rare, autosomal dominant disease. There are two clinical types of BPES: type I patients have eyelid abnormalities accompanied by infertility in affected females, while type II patients only display eyelid malformations. Previous studies have reported that the forkhead box L2 (FOXL2) gene mutations cause BPES.

Purpose

To identify plausible FOXL2 mutation in a Chinese family with BPES and infertility

Methods

Mutational screening of FOXL2 was performed in the affected members and 223 controls. Functional characterization of the novel mutation identified was carried out in vitro by luciferase reporter assay and subcellular localization experiment.

Results

A novel heterozygous mutation c.188 T > A (p.I63N) in FOXL2 was identified in two BPES patients in this family. The mutation abolished the transcriptional repression of FOXL2 on the promoters of CYP19A1 and CCND2 genes, as shown by luciferase reporter assays. However, no dominant-negative effect was observed for the mutation, and it did not impact FOXL2 protein nuclear localization and distribution.

Conclusions

The mutation c.188 T > A (p.I63N) in FOXL2 might be causative for BPES and infertility in this family and further amplified the spectrum of FOXL2 mutations.

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Acknowledgments

The authors thank the patients for their participation. This work was supported by grants from the National Key Research & Developmental Program of China (2017YFC1001100), National Natural Science Foundation of China (81571505, 81571406 and 81873823), Shandong Medical and Health Science and Technology Development Project (2017WS741), Young Scholars Program of Shandong University (2016WLJH26), and the Fundamental Research Funds of Shandong University.

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Authors and Affiliations

  1. Center for Reproductive Medicine, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory of Reproductive Endocrinology, Ministry of Education, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, China

    Jingmei Hu, Hanni Ke, Wei Luo, Yajuan Yang, Hongli Liu, Guangyu Li, Yingying Qin, Jinlong Ma & Shidou Zhao

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  1. Jingmei Hu
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  2. Hanni Ke
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  3. Wei Luo
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Correspondence to Shidou Zhao.

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Hu, J., Ke, H., Luo, W. et al. A novel FOXL2 mutation in two infertile patients with blepharophimosis–ptosis–epicanthus inversus syndrome. J Assist Reprod Genet 37, 223–229 (2020). https://doi.org/10.1007/s10815-019-01651-2

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