A locus for primary lateral sclerosis on chromosome 4ptel-4p16.1

Background: Primary lateral sclerosis (PLS) is an adult-onset upper motor neuron disease resulting in spinal and bulbar spasticity. A family with 8 individuals diagnosed with PLS was previously reported. Objective: To identify a locus for a large family with PLS. Methods: A 550-marker whole-genome scan was performed on this family followed by fine mapping with sequence-tagged site markers to identify a candidate region. Results: A locus was identified for this family between the telomere of chromosome 4 and marker D4S2928 (4ptel-4p16.1). A maximum lod score of 3.01 was obtained for marker D4S2936. The region spans 23.17 cM (10.2 megabase pairs) and encompasses 130 genes. Conclusions: PLS1 does not map near any other identified loci for upper or lower motor neuron diseases and thus represents a novel locus for PLS.