UC San Diego

Kallman’s syndrome is an anosmic subtype of Isolated Gonadotropin releasing hormone Deficiency (IGD) and causes abnormal puberty and infertility. The etiology of Kallman’s syndrome is still not well understood; recently, a genetic approach has been taken towards elucidating how Kallman’s syndrome alters gonadotropin-releasing hormone (GnRH) neuron migration and hormone secretion patterns. An exome-wide association study has identified a single nucleotide polymorphism in DLX1 to be associated with IGD. To characterize functional consequences a mutation of DLX1 in vitro, we developed a patient mutation model in mature and developing immortalized GnRH neuron cell lines. We observed that the IGD patient mutation of an insertion of an adenine in the 380th base pair of the DLX1 gene leads to impaired homeodomain binding site activation and lower GnRH expression.