Biallelic PTRHD1 Frameshift Variants Associated with Intellectual Disability, Spasticity, and Parkinsonism

Ghalia Al-Kasbi, Abeer Al-Saegh, Ahmed Al-Qassabi, Tariq Al-Jabry, Fahad Zadjali, Said Al-Yahyaee, Almundher Al-Maawali*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1253-1257
Number of pages5
JournalMovement Disorders Clinical Practice
Issue number8
Publication statusPublished - Nov 2021


  • PTRHD1
  • intellectual disability
  • parkinsonism

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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