Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia

Taneli Raivio, Magdalena Avbelj, Mark J. McCabe, Christopher J. Romero, Andrew A. Dwyer, Johanna Tommiska, Gerasimos P. Sykiotis, Louise C. Gregory, Daniel Diaczok, Vaitsa Tziaferi, Mariet W. Elting, Raja Padidela, Lacey Plummer, Cecilia Martin, Bihua Feng, Chengkang Zhang, Qun Yong Zhou, Huaibin Chen, Moosa Mohammadi, Richard QuintonYisrael Sidis, Sally Radovick, Mehul T. Dattani, Nelly Pitteloud

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


Context: Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain. Objective: The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins. Design and Participants: A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in gene simplicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro. Results: Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C>T, p.T112T). One patient had a synonymous change in FGF8 (c.216G>A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C). Conclusions: Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/ SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain.

Original languageEnglish (US)
Pages (from-to)E694-E699
JournalJournal of Clinical Endocrinology and Metabolism
Issue number4
StatePublished - Apr 2012
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia'. Together they form a unique fingerprint.

Cite this