Background: PTRHD1 was proposed as a disease-causing gene of intellectual disability, spasticity, and parkinsonism.
Objectives: To characterize the clinical phenotype and the molecular cause of intellectual disability in four affected individuals of a consanguineous family.
Methods: Clinical evaluation, whole-exome sequencing, Sanger sequencing, reverse transcription polymerase chain reaction (PCR), real-time PCR, immunoblot, and isoelectric focusing.
Results: A homozygous 28-nucleotide frameshift deletion introducing a premature stop codon in the PTRHD1 exon 1 was identified in the four affected members. We further confirmed the apparent transcript escape of the nonsense-mediated messenger RNA (mRNA) decay pathway. Real-time PCR showed that mRNA expression of the mutant PTRHD1 is higher compared to the wild-type. Western blotting and isoelectric focusing identified a truncated, but stable mutant PTRHD1 protein expressed in the patient's primary cells.
Conclusions: We provide further evidence that PTRHD1 mutations are associated with autosomal-recessive childhood-onset intellectual disability associated with spasticity and parkinsonism.
Keywords: PTRHD1; intellectual disability; parkinsonism.
© 2021 International Parkinson and Movement Disorder Society.