TY - JOUR
T1 - Biallelic PTRHD1 Frameshift Variants Associated with Intellectual Disability, Spasticity, and Parkinsonism
AU - Al-Kasbi, Ghalia
AU - Al-Saegh, Abeer
AU - Al-Qassabi, Ahmed
AU - Al-Jabry, Tariq
AU - Zadjali, Fahad
AU - Al-Yahyaee, Said
AU - Al-Maawali, Almundher
N1 - Funding Information:
This work was supported by His Majesty Trust Funds at the Sultan Qaboos University; study code: SR/MED/GENT/16/01. The authors declare that there are no conflicts of interest relevant to this work.
Publisher Copyright:
© 2021 International Parkinson and Movement Disorder Society
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - PTRHD1
KW - intellectual disability
KW - parkinsonism
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U2 - 10.1002/mdc3.13342
DO - 10.1002/mdc3.13342
M3 - Article
C2 - 34765690
AN - SCOPUS:85115063957
SN - 2330-1619
VL - 8
SP - 1253
EP - 1257
JO - Movement Disorders Clinical Practice
JF - Movement Disorders Clinical Practice
IS - 8
ER -