Two Families With Amyotrophic Lateral Sclerosis Founder Mutation TARDBP p.G298S in Hong Kong

Amyotrophic lateral sclerosis (ALS), which is characterized by progressive deterioration of upper and lower motor neurons resulting in severe muscle atrophy, respiratory failure, and death, is a rare and fatal neurodegenerative disease. TARDBP p.G298S was recently identified as a founder mutation in southern Chinese. This article first presented case summaries of three ALS patients: two families with TARDBP p.G298S presenting with heterogeneous clinical phenotypes, including a case with an unusual extraocular muscle onset. A review of TARDBP p.G298S cases reported worldwide was conducted, surveying the age and site of onset, disease duration, and motor neuron involvement. Finally, an overview of genetic mutations reported locally for ALS was presented, showing that TARDBP p.G298S is a common mutation detected in this locality. This article highlighted the distinct clinical manifestations and genetic background in ALS patients and will be useful for developing genetic screening and counseling strategies in Hong Kong and southern China.