Ghalia Al-Kasbi1, Abeer Al-Saegh1,2, Ahmed Al-Qassabi3, Tariq Al-Jabry1, Fahad Zadjali4, Said Al-Yahyaee1, Almundher Al-Maawali1. 1. Department of Genetics, College of Medicine and Health Sciences Sultan Qaboos University Muscat Oman. 2. Genetic and Developmental Medicine Clinic Sultan Qaboos University Hospital Muscat Oman. 3. Department of Medicine, Neurology Unit Sultan Qaboos University Hospital Muscat Oman. 4. Department of Clinical Biochemistry, College of Medicine and Health Sciences Sultan Qaboos University Muscat Oman.
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.
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.
Authors: Demy J S Kuipers; Jonathan Carr; Soraya Bardien; Pearl Thomas; Boiketlo Sebate; Guido J Breedveld; Rick van Minkelen; Rutger W W Brouwer; Wilfred F J van Ijcken; Marjon A van Slegtenhorst; Vincenzo Bonifati; Marialuisa Quadri Journal: Mov Disord Date: 2018-11-06 Impact factor: 10.338
Authors: Guillermina Rosas-Sandoval; Alexandre Ambrogelly; Jesse Rinehart; David Wei; L Rogelio Cruz-Vera; David E Graham; Karl O Stetter; Gabriel Guarneros; Dieter Söll Journal: Proc Natl Acad Sci U S A Date: 2002-12-10 Impact factor: 11.205