Kallmann syndrome (KS) is defined by the combination of isolated hypogonadotrophic hypogonadism (IHH) and anosmia, with renal agenesis occurring in 30% of KS cases with KAL1 gene mutations.
A defective anosmin-1 molecule may also play a role in the development of synkinesia and renal agenesis, which are exclusively seen in the X-linked form of KS.
A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1).
Although loss-of-function mutations of the KAL1 gene is associated with the X-linked form of KS, the reproductive capacity remains unidentified in patients with KS with KAL1 gene mutations.
Although loss-of-function mutations of the KAL1 gene is associated with the X-linked form of KS, the reproductive capacity remains unidentified in patients with KS with KAL1 gene mutations.
Although multiple genetic pathways are now known to be involved in the development of this disorder, KAL1, the gene causing the X-linked form of Kallmann syndrome was the first to be identified.
Anosmin-1, the KAL-1 gene product underlying X-linked KS, modulates FGFR1 signalling via regulation of FGF2/FGFR1/heparin signalling complex assembly and activity.
As a consequence of this mutation, the function of the KAL1 protein consisting of 680 amino acids was severely truncated so as to be consistent with Kallmann syndrome.
Based on the distribution of anosmin-1 in the early olfactory system, the pathogenesis of the olfactory loss and GnRH deficiency in X-linked Kallmann syndrome is discussed.
Clinical assessment and mutation analysis of Kallmann syndrome 1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1, or KAL2) in five families and 18 sporadic patients.