A Compound Heterozygote for GCH1 Mutation Represents a Case of Atypical Dopa-Responsive Dystonia

In this study, the entireGCH1 gene was screened in 14 Indian DRD patients and their family members. A family was identified where the proband was found to be a compound heterozygote forGCH1 (p.R184H and p.V204I) variants; the former variant being inherited from the father and the latter from the mother. All other family members harboring one of theseGCH1 variants were asymptomatic except for one (heterozygous for p.R184H) who was diagnosed with DRD. In silico analyses predicted these two variants to be pathogenic and disruptive to GCH1enzymatic activity. This proband was misdiagnosed as cerebral palsy and remained untreated for 25  years. He developed retrograde movements and gait problems in lower limbs, deformity in upper limbs, and difficulty in swallowing, and became mute. However, most of his symptoms were alleviated upon levodopa administration. Our study confirms the variability of DRD phenotype and the reduced penetr ance ofGCH1 mutations. It also emphasizes the need of molecular diagnostic test and L-dopa trial especially for those with atypical DRD phenotype.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research