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.