A novel deletion in RMST implicates the loss of function of a lncRNA as a unique cause of KS and suggests it plays a critical role in the ontogeny of GnRH neurons and puberty.
These findings provide new insights into GnRH-1 and OECs development and demonstrate that human <i>GLI3</i> mutations contribute to KS etiology.<b>Significance statement.</b> The transcription factor Gli3 is necessary for correct development of the olfactory system.
We here determine that Six3 is haploinsufficient for MOE development, GnRH neuron migration, and fertility, and represents a novel candidate gene for Kallmann syndrome, a form of inherited infertility.
Fibroblast growth factor receptor 1 (FGFR1), a tyrosine kinase receptor, was one of the first genes whose mutations were identified as causative in KS FGFR1 is responsible for the formation of the GnRH neuron system.
It leads to early diagnosis of KS and will benefit the relevant patient care.The KS diagnosis should be done at an early stage, but symptoms and clinical manifestations are not always evident both in ENT and pediatric field.
Our data indicate that TSHZ1 is a key regulator of mammalian OB development and function and controls the expression of molecules involved in human Kallmann syndrome.
Three missense AXL mutations (p.L50F, p.S202C, and p.Q361P) and one intronic variant 6 bp upstream from the start of exon 5 (c.586-6 C>T) were identified in two KS and 2 two nIHH subjects.
We report a female with combined pituitary hormone deficiencies (GH, TSH, gonadotropin and ACTH), except for prolactin, as a consequence of PROP1 mutation, and a male with KS (anosmia and IHH) due to Kal 2 gene (fibroblast growth factor receptor 1- FGFR1) mutation, both of whom in adulthood presented with prolactinomas.
We report a female with combined pituitary hormone deficiencies (GH, TSH, gonadotropin and ACTH), except for prolactin, as a consequence of PROP1 mutation, and a male with KS (anosmia and IHH) due to Kal 2 gene (fibroblast growth factor receptor 1- FGFR1) mutation, both of whom in adulthood presented with prolactinomas.
Results of isothermal titration calorimetry experiments show the KS mutation causes a 10-fold decrease in heparin binding affinity and also a complete loss in ligand (FGF-1) binding.
In this study, for the first time, the molecular basis for the FGFR associated KS mutation (A168S) is elucidated using a variety of biophysical experiments, including multidimensional NMR spectroscopy.
The identified deletion included ANK1, but not FGFR1, which is consistent with the absence of any phenotype or laboratory findings of Kallmann syndrome.
Strikingly, mice lacking SEMA3A or semaphorin signalling through both NRP1 and NRP2 recapitulate the anatomical features of a single case of KS analysed so far, and may therefore be used as genetic models to elucidate the pathogenesis of KS.
Strikingly, mice lacking SEMA3A or semaphorin signalling through both NRP1 and NRP2 recapitulate the anatomical features of a single case of KS analysed so far, and may therefore be used as genetic models to elucidate the pathogenesis of KS.