Analysis of KAL1, FGFR1, GPR54, and NELF copy number variations by multiplex ligation dependent probe amplification in male patients with idiopathic hypogonadotropic hypogonadism

Aim: Hypogonadotropic hypogonadism is a production failure of gonadal hormones due to a lack of gonadotropin secretion. Here, we aimed to determine the prevalence of genomic rearrangements in the KAL1, FGFR1, GPR54, and NELF genes in patients diagnosed with hypogonadotropic hypogonadism. Materials and methods: The study included 86 male patients with idiopathic hypogonadotropic hypogonadism (76 diagnosed with normosmic idiopathic hypogonadotropic hypogonadism and 10 with Kallmann syndrome). Additionally, 95 healthy controls were recruited to investigate rearrangements in the KAL1, FGFR1, GPR54, and NELF genes, using multiplex ligation dependent probe amplification. Results: From the 86 patients, 3 patients with Kallmann syndrome had heterozygous deletions in exon 9 of the KAL1 gene (probe target sequence: 5941-L05940), and 1 of these patients also had a duplication in exon 11 of the same gene (probe target sequence: 4427-L03813). Additionally, 1 patient with nIHH had a duplication in exons 14 and 18 of the FGFR1 gene (probe target sequences: 4440-L03826 and 4441-L03827, respectively). No deletions/duplications were identified in the GPR54 and NELF genes and no genomic rearrangement was detected in the control subjects. Conclusion: To improve our understanding of this complex condition and also for better genetic counseling and directing therapy, defining the genetic basis of these disorders is essential.