title: A mutation in the follicle-stimulating hormone receptor as a cause of familial spontaneous ovarian hyperstimulation syndrome.
abstract: Ovarian hyperstimulation syndrome (OHSS) occurs mainly after excessive stimulation of the ovaries by exogenous gonadotropins administrated in the context of in vitro fertilization procedures (iatrogenic OHSS). Recently, spontaneous and recurrent occurrence of the disease (spontaneous OHSS) was shown in two families to be caused by mutations affecting the follitropin receptor (FSHr). The two mutant FSHr (T449I, D567N) harbor aminoacid substitutions in the serpentine portion of the receptor and display abnormally high sensitivity to the pregnancy hormone hCG, thus providing a satisfactory explanation to the phenotype. In addition, mutant D567N showed also increased sensitivity to thyrotopin (TSH) and displayed increase in basal (ligand-independent) activity. In this report, we describe a new familial case of recurrent OHSS. The affected women were heterozygous for a different mutation involving codon 449, where an alanine was substituted for threonine. Similar to D567N, the T449A FSHr mutant shows an increase of its sensitivity to both hCG and TSH, together with an increase in basal activity. Together with the two previous studies, this report shows that inappropriate stimulation of the FSHr by hCG is a cause of spontaneous OHSS.
authors.affiliation: IRIBHM, ULB, Brussels, Belgium.
authors.forename: Lucia
authors.initials: L
authors.lastname: Montanelli
authors.forename: Anne
authors.initials: A
authors.lastname: Delbaere
authors.forename: Costantino
authors.initials: C
authors.lastname: Di Carlo
authors.forename: Carmine
authors.initials: C
authors.lastname: Nappi
authors.forename: Guillaume
authors.initials: G
authors.lastname: Smits
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vassart
authors.forename: Sabine
authors.initials: S
authors.lastname: Costagliola
mesh_terms: D000328:Adult; D000818:Animals; D019556:COS Cells; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D016471:Ovarian Hyperstimulation Syndrome / Q000235:genetics*; D017354:Point Mutation; D011247:Pregnancy; D011962:Receptors, FSH / Q000235:genetics* / Q000378:metabolism; D012008:Recurrence; D017422:Sequence Analysis, DNA; D014162:Transfection
chemical_list: D011962:Receptors, FSH; D000242:Cyclic AMP