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. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 28-year-old mother with normosmic IHH gave birth to MZ twin boys after a transfer of a single frozen-thawed embryo. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): Phenotypic features of the subjects. RESULT(S): 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. CONCLUSION(S): 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. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 28-year-old mother with normosmic IHH gave birth to MZ twin boys after a transfer of a single frozen-thawed embryo. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): Phenotypic features of the subjects. RESULT(S): 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. CONCLUSION(S): 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. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.