The PUM1 gene contributes to the development and function of neurons (brain cells). When the PUM1 protein is unable to function properly due to a mutation in the gene, different cognitive and motor problems can ensue, depending on how severe the mutation is.
A mutation that impairs PUM1 function more strongly produces Pumilio1-associated developmental disability, ataxia, and seizures (PADDAS), which is a condition present from birth. Affected children may have developmental delay that affects language or cognitive skills; they may also have seizures (fits or transitory periods of looking unfocused, “out of it”), ataxia (unsteady gait), and ptosis (drooping eyelids). Not all people with a change in the PUM1 gene have all these features. PUM1-related disorders can affect both males and females.
A mutation that impairs PUM1 function only slightly can produce an adult-onset condition called Pumilio1-related cerebellar ataxia (PRCA). Several generations of one family have been described with PRCA. These individuals have normal intelligence and neurological function when younger, but with increasing age some older individuals developed ataxia (an unsteady gait) that eventually required the use of a walker.
Since PUM1-related conditions were first described in twenty individuals in 2017, fifteen additional individuals have been reported in the medical literature. As more individuals are diagnosed with PUM1-related disorders, we will learn more about these conditions.