Consanguineous Chinese Familial Study Reveals that a Gross Deletion that Includes the SYCE1 Gene Region Is Associated with Premature Ovarian Insufficiency
Premature ovarian insufficiency (POI) is a highly heterogeneous ovarian disorder. Genetic factors account for the cause of POI. We aimed to analyze the genetic alterations in two affected sisters diagnosed with POI and their parents from a highly consanguineous Chinese Han family. Whole-exome sequencing was performed, and bioinformatics analysis was used to determine the potential genetic cause of POI in this family. A SYCE1 deletion was verified by Sanger sequencing. A homozygous deletion in SYCE1 was harbored by the proband and her affected sister, whereas both parents had heterozygous deletions. There were distinct differences in the amino acid sequences between wild-type and SYCE1 deletion. Domain analysis and 3D structural analysis of the SYCE1 deletion was also performed to evaluate the potential impact and pathogenicity of POI. The SYCE1 domain structure was truncated. Additionally, the 3D structure showed that the SYCE1 deletion changed the shape of the protein compared with that of wild-type SYCE1. This study revealed a novel SYCE1 deletion. This SYCE1 deletion may be the cause of POI. Genetic counseling for POI is helpful for researchers and clinicians to identify the mode of genetic inheritance for SYCE1 deletion in POI pathology.
KeywordsPremature ovarian insufficiency Whole-exome sequencing SYCE1
We sincerely thank the affected patients and their parents for their participation in this study. We are also grateful to all the clinical investigators for collecting patient information. We acknowledge Zaiwei Zhou, PhD, and Wenping Qu for assisting with the bioinformatics analysis. We thank American Journal Experts for its linguistic assistance during the preparation of this manuscript. The work reported in this article was completed at the Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University.
Jing Zhe conceived and designed the study, collected the data, performed the data analysis and interpretation, and drafted and revised the manuscript. Desheng Ye, Xin Chen, Yudong Liu, Xingyu Zhou, Ying Li, and Jun Zhang collected the data. Shiling Chen designed the study, revised the manuscript, and approved the final version for publication.
The author(s) disclose the receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by grants from the National Key Research & Developmental Program of China (2017YFC1001103) and the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education under grant LC2016ZD010.
Compliance with Ethical Standards
This study was approved by Medical Ethics Committee of Nanfang Hospital, Southern Medical University (NFEC-2017-197). Written informed consent was obtained from all participating individuals.
Conflict of Interest
The authors declare that they have no conflict of interest.