A novel mutation in SOX2 causes hypogonadotropic hypogonadism with mild ocular malformation

Masaki Takagi, Satoshi Narumi, Yumi Asakura, Koji Muroya, Yukihiro Hasegawa, Masanori Adachi, Tomonobu Hasegawa

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


Background: Heterozygous SOX2 mutations have been reported to cause isolated hypogonadotropic hypogonadism (HH) in addition to ocular and brain abnormalities. Objective: We report a novel missense SOX2 (Y110C) mutation in an HH patient with mild ocular malformation. Patients: The 20-year-old male was referred because of typical signs of complete hypogonadism, with small intrascrotal testes (2 ml), no pubic hair (P1), and a micropenis. Hormone assays revealed very low plasma testosterone levels and very low levels of plasma gonadotropin. He was found to have retinal detachment in his right eye and surgery was performed at the age of 14 years. Results: Using a next-generation sequencing strategy, we identified a novel heterozygous SOX2 mutation, c.329A>G (p.Y110C). Y110C SOX2 had reduced transactivation and no dominant negative effect. Subcellular localization revealed no significant difference between wild-type and mutant SOX2. EMSA experiments showed that the Y110C SOX2 abrogated DNA-binding ability. Conclusion: The Y110C mutation affects a critical residue in the SOX2 protein. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in SOX2. When multiple genes need to be analyzed for mutations simultaneously, targeted sequence analysis of interesting genomic regions is an attractive approach.

Original languageEnglish
Pages (from-to)133-138
Number of pages6
JournalHormone Research in Paediatrics
Issue number2
Publication statusPublished - 2014 Mar


  • HMG domain
  • Hypogonadotropic hypogonadism
  • SOX2
  • Targeted next-generation sequencing

ASJC Scopus subject areas

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


Dive into the research topics of 'A novel mutation in SOX2 causes hypogonadotropic hypogonadism with mild ocular malformation'. Together they form a unique fingerprint.

Cite this