Idiopathic hypogonadotropic hypogonadism in a mother and her monozygotic twins born after a single embryo transfer.
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.
Laitinen
Eeva-Maria
EM
Institute of Biomedicine, Department of Physiology, University of Helsinki, Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland.
Tommiska
Johanna
J
Dunkel
Leo
L
Sankilampi
Ulla
U
Vaaralahti
Kirsi
K
Raivio
Taneli
T
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
C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1