Abstract: To explore the genetic basis of a patient with hypergonadotropic amenorrhea and normal number of antral follicles, and provide a basis for genetic counseling and direction for reproduction, the proband was subjected to whole exome sequencing and her sister, brother and parents performed sanger sequencing on FSHR gene mutation loci. We applied the bioinformatics analysis according to clinical characterization of the patient. The proband was found to harbor compound heterozygous variants of the FSHR gene in exon 5 c.392G>A (p.Gly131Asp) and exon 4 c.301A>G (p.Lys104Glu), which were respectively inherited from her mother and father. The sister and brother were found to have the same FSHR gene complex heterozygous variation as the patient. Pedigree and bioinformatic analysis suggested that both mutations were likely pathogenic according to the ACMG guidelines. The clinical data and literature review suggested that the patient was affected with resistant ovary syndrome rather than premature ovarian failure. In this study, FSHR gene compound heterozygous variation was identified as a possible genetic cause of primary amenorrhea and infertility in the patient and her sister. Infertility is a kind of disease with very high genetic heterogeneity, and it is difficult to distinguish the diseases by routine detection in clinical practice. Genetic detection is of great significance for the detection of such diseases. At the same time, few pathogenic variants of FSHR gene have been reported in Chinese population. The detection of two new mutation sites of FSHR gene in the family of ovarian resistance syndrome in this paper enriches the mutation spectrum of FSHR gene, which has important reference significance for the diagnosis of this disease in the future.
Key words: FSHR gene; compound heterozygous variant; infertility; resistant ovary syndrome; primary amenorrhea
（Acta Laser Biology Sinica, 2021, 30(4): 378-384）