Genetic analysis of novel pathogenic gene HROB in primary ovarian insufficiency.

A 13-year and 6-month old girl attended the Hunan Children's Hospital due to delayed menarche. The laboratory test results indicated an increased follicle-stimulating hormone and luteinizing hormone, decreased anti-Mullerian hormone, and pelvic ultrasound showed a cord-like uterus and absence of bilateral ovaries. Her 11-year and 5-month old younger sister had the same laboratory and imaging findings, and both girls were diagnosed as primary ovarian insufficiency. Whole exome sequencing and Sanger sequencing confirmed that the proband and her sister carried heterozygous variants of gene c.718C>T (p.Arg240*) and c.1351C>T (p.Arg451*), which were inherited from their parents respectively and consistent with autosomal recessive inheritance. Oral estradiol valerate at an initial dose of 0.125 mg/d was given to the proband, and the secondary sexual characteristics and uterine development were monitored.