Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

FSH Receptor Deficiency [N97.9]

OMIM numbers: 233300136435 (FSHR)

Dr. rer. nat. Annett Wagner, Dr. med. Dagmar Wahl

Scientific Background

The follicle-stimulating hormone (FSH) stimulates estrogen production in the granulosa cells and therefore plays a major role in the hypothalamic hypophyseal regulated maturation of the ovum in the ovaries. In men, FSH is involved in the maturation of the spermatozoa in the testes. The FSH receptor deficiency (FSHR deficiency) is a rare disorder that leads to delayed puberty, primary amenorrhea and infertility in women and to a disorder of the spermatogenesis in men.

FSHR deficiency is inherited in an autosomal recessive manner. The FSHR gene is located on chromosome 2p16.3, comprises 10 exons and encodes for a protein with 695 amino acids. Mutations in the FSHR gene can be categorized into three groups according to their functions: activating, inactivating and neutral mutations. Activating mutations cause a higher response of the FSH receptor to FSH, which may result in ovarian hyperstimulation syndrome. Inactivating mutations, however, cause a lower FSH response, usually resulting in a compensatory increase of FSH in the serum. According to the current state of knowledge, neutral mutations do not have any functional significance.