Hypothalamic dysfunction in a female with isolated hypogonadotropic hypogonadism and compound heterozygous TACR3 mutations and clinical manifestation in her heterozygous mother

Maki Fukami, Tetsuo Maruyama, Sumito Dateki, Naoko Sato, Yasunori Yoshimura, Tsutomu Ogata

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15 Citations (Scopus)


Background/Aims:TAC3 and TACR3 have recently been shown to be causative genes for an autosomal recessive form of isolated hypogonadotropic hypogonadism (IHH). Here, we report a Japanese female with IHH and compound heterozygous TACR3 mutations and her heterozygous parents, and discuss the primary lesion for IHH and clinical findings. Case Report: This female was identified through mutation analysis of TAC3 and TACR3 in 57 patients with IHH. At 24 years of age, an initial standard GnRH test showed poor gonadotropin response (LH <0.2-0.6 IU/l), whereas the second GnRH test performed after GnRH priming (100 μg i.m. for 5 consecutive days) revealed ameliorated gonadotropin responses (LH 0.3-6.4 IU/l; FSH 2.2-9.6 IU/l). The mother exhibited several features suggestive of mild IHH, whereas the father showed an apparently normal phenotype. Results: She had a paternally derived nonsense mutation at exon 1 (Y145X) and a maternally inherited single nucleotide (G) deletion from the conserved 'GT' splice donor site of intron 1 (IVS1+1delG). Conclusions: The results suggest hypothalamic dysfunction as the primary cause for IHH in patients with biallelic TACR3 mutations and clinical manifestation in heterozygous females, together with the rarity of TAC3 and TACR3 mutations in patients with IHH.

Original languageEnglish
Pages (from-to)477-481
Number of pages5
JournalHormone Research in Paediatrics
Issue number6
Publication statusPublished - 2010 May 1



  • Heterozygous manifestation
  • Hypogonadotropic hypogonadism
  • Hypothalamus
  • TACR3 mutation

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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