Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Al-Kasbi G

PROVIDER: S-EPMC8564806 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Biallelic <i>PTRHD1</i> Frameshift Variants Associated with Intellectual Disability, Spasticity, and Parkinsonism.

Al-Kasbi Ghalia G Al-Saegh Abeer A Al-Qassabi Ahmed A Al-Jabry Tariq T Zadjali Fahad F Al-Yahyaee Said S Al-Maawali Almundher A

Movement disorders clinical practice 20210920 8

<h4>Background</h4><i>PTRHD1</i> was proposed as a disease-causing gene of intellectual disability, spasticity, and parkinsonism.<h4>Objectives</h4>To characterize the clinical phenotype and the molecular cause of intellectual disability in four affected individuals of a consanguineous family.<h4>Methods</h4>Clinical evaluation, whole-exome sequencing, Sanger sequencing, reverse transcription polymerase chain reaction (PCR), real-time PCR, immunoblot, and isoelectric focusing.<h4>Results</h4>A h ...[more]

PMID: 34765690

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