Molecular Diagnosis of Kallmann Syndrome by Whole Exon Sequencing and Bioinformatic Approaches 

Abstract Background: Kallmann syndrome is a hypogonadotropic hypogonadism accompanied by anosmia or hypoxia. More than 10 Kallmann syndrome pathogenic genes have been found. However, only 30% of the incidence of Kallmann syndrome is related to the above genes, suggesting that there are other disease-related genes of KS that have not been found. Methods： We studied Kallmann syndrome pathogenesis through high-throughput exome sequencing on four patients with Kallmann syndrome for screening the potential pathogenic sites and exploring the genotype-phenotype correlation. Clinical data and peripheral blood samples were collected from the patients. White blood cells were separated and genomic DNA was extracted. High-throughput sequencing of all exons in the candidate pathogenic genes of the probands was performed, and the results obtained were analyzed. Results: Sequencing revealed mutations in the KLB, p.T313M, ANOS1, p.C172F, and IGSF10 (p.Lys1819Arg and p.Arg1035Thr) at different sites, which may have been associated with disease onset. Discovery of these sites can improve our understanding of KS pathogenesis and serve as a novel target in further studies on KS. Conclusion: our analysis found new mutation sites to facilitate follow-up research. Diagnosis of Kallmann syndrome is a challenging, timely diagnosis and treatment can induce puberty, thereby improving sexual, bone, metabolic, and mental health.