Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies

The gene POLR3B is associated with 4H leukodystrophy, a syndrome that includes reproductive failure (in the form of idiopathic hypogonadotropic hypogonadism (IHH)), neurologic disease (often in the form of ataxia), and hypodontia. To date, most patients reported to carry biallelic variants in POLR3B begin to show neurologic symptoms in early childhood, often before they are 3 years old. In our cohort of 565 patients with IHH, we identified four individuals with two variants in POLR3B; however, these patients were not found to have any signs of neurodegeneration or ataxia when evaluated in their early 30s. Our finding broadens the understanding of the spectrum of reproductive and neurologic disorders associated with POLR3B mutations. (By Mary Richards, http://jmg.bmj.com/content/early/2016/08/10/jmedgenet-2016-104064 )