title: Idiopathic hypogonadotropic hypogonadism in a mother and her monozygotic twins born after a single embryo transfer.
abstract: OBJECTIVE
  To describe a mother with idiopathic hypogonadotropic hypogonadism (IHH) and her monozygotic (MZ) twin boys who all have the same heterozygous fibroblast growth factor receptor-1 (FGFR1) gene mutation.
  
  
  METHODS
  Case report.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  A 28-year-old mother with normosmic IHH gave birth to MZ twin boys after a transfer of a single frozen-thawed embryo.
  
  
  METHODS
  Clinical and biochemical evaluation of IHH. Sequence analysis of the 17 coding exons (exons 2-18) and exon-intron boundaries of FGFR1 from polymerase chain reaction-amplified genomic DNA from peripheral blood leukocytes of the subjects.
  
  
  METHODS
  Phenotypic features of the subjects.
  
  
  RESULTS
  All subjects harbored a previously undescribed heterozygous FGFR1 mutation (c.2049-1 G-->C), leading to the skipping of exon 16 and thus a loss of amino acids 684-726 in the tyrosine kinase domain of the receptor. The absence of exon 16 was verified at the cDNA level. The twins manifested with microphallus, cryptorchidism, and deficient postnatal activation of the hypothalamic-pituitary-gonadal axis, findings consistent with IHH.
  
  
  CONCLUSIONS
  Our report underlines that assisted reproductive techniques enable the inheritance of gene mutations causing infertility. This is the first report on the phenotypic features of MZ twins with an FGFR1 mutation.
authors.affiliation: Institute of Biomedicine, Department of Physiology, University of Helsinki, Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Eeva-Maria
authors.initials: EM
authors.lastname: Laitinen
authors.forename: Johanna
authors.initials: J
authors.lastname: Tommiska
authors.forename: Leo
authors.initials: L
authors.lastname: Dunkel
authors.forename: Ulla
authors.initials: U
authors.lastname: Sankilampi
authors.forename: Kirsi
authors.initials: K
authors.lastname: Vaaralahti
authors.forename: Taneli
authors.initials: T
authors.lastname: Raivio
mesh_terms: D000328:Adult; D004200:Diseases in Twins / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007006:Hypogonadism / Q000175:diagnosis* / Q000235:genetics; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D008297:Male; D008431:Maternal-Fetal Exchange / Q000235:genetics; D009035:Mothers; D036801:Parturition; D011247:Pregnancy; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D056826:Single Embryo Transfer; D014430:Twins, Monozygotic
chemical_list: C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1