BackgroundKallmann syndrome (KS), comprised of congenital hypogonadotropic hypogonadism (HH) and anosmia, is a clinically and genetically heterogeneous disorder. Its exact incidence is currently unknown, and a mutation in one of the identified KS genes has only been found in ~30% of the patients.MethodsHerein, we investigated epidemiological, clinical, and genetic features of KS in Finland.ResultsThe minimal incidence estimate of KS in Finland was 1:48 000, with clear difference between males (1:30 000) and females (1:125 000) (p = 0.02). The reproductive phenotype of 30 probands (25 men; 5 women) ranged from severe HH to partial puberty. Comprehensive mutation analysis of all 7 known KS genes (KAL1, FGFR1, FGF8, PROK2, PROKR2, CHD7, and WDR11) in these 30 well-phenotyped probands revealed mutations in KAL1 (3 men) and FGFR1 (all 5 women vs. 4/25 men), but not in other genes.ConclusionsOur results suggest that Finnish KS men harbor mutations in gene(s) yet-to-be discovered with sex-dependent penetrance of the disease phenotype. In addition, some KS patients without CHD7 mutations display CHARGE-syndrome associated phenotypic features (e.g. ear or eye anomalies), possibly implying that, in addition to CHD7, there may be other genes associated with phenotypes ranging from KS to CHARGE.

Abstract:The induction of epithelial-to-mesenchymal transition (EMT) in human lung epithelial cell lines was investigated after α-particle and γ-radiation exposures. We applied TGF-β treatment of cells as positive EMT-controls and tested in parallel if radiation has a potentiating effect on the EMT induction. BEAS-2B and HBEC-3KT cells were irradiated with 5.4 MeV α-particles or γ-rays ( 60 Co, 1.13-1.15 Gy/min) with or without of TGF-β. The cells were harvested three days post treatment and the EMT markers vimentin, fibronectin and E-cadherin were analysed by immunofluorescence staining and Western blotting. The TGF-β treatment-induced EMT in both cell lines in the applied concentrations. We could not prove any clear EMT induction with low or moderate doses of α-particles and γ-rays. No significant additive effect with radiation and TGF-β was observed. We suggest that there might be a different mechanism induced by radiation in bronchial cells after radon and medical exposures that does not involve direct EMT changes.

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