Al-Kasbi Ghalia, Al-Saegh Abeer, Al-Qassabi Ahmed, Al-Jabry Tariq, Zadjali Fahad, Al-Yahyaee Said, Al-Maawali Almundher
Department of Genetics, College of Medicine and Health Sciences Sultan Qaboos University Muscat Oman.
Genetic and Developmental Medicine Clinic Sultan Qaboos University Hospital Muscat Oman.
Mov Disord Clin Pract. 2021 Sep 20;8(8):1253-1257. doi: 10.1002/mdc3.13342. eCollection 2021 Nov.
was proposed as a disease-causing gene of intellectual disability, spasticity, and parkinsonism.
To characterize the clinical phenotype and the molecular cause of intellectual disability in four affected individuals of a consanguineous family.
Clinical evaluation, whole-exome sequencing, Sanger sequencing, reverse transcription polymerase chain reaction (PCR), real-time PCR, immunoblot, and isoelectric focusing.
A homozygous 28-nucleotide frameshift deletion introducing a premature stop codon in the 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 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.
We provide further evidence that PTRHD1 mutations are associated with autosomal-recessive childhood-onset intellectual disability associated with spasticity and parkinsonism.
被认为是智力残疾、痉挛和帕金森症的致病基因。
对一个近亲家庭中四名受影响个体的智力残疾临床表型和分子病因进行特征描述。
临床评估、全外显子组测序、桑格测序、逆转录聚合酶链反应（PCR）、实时PCR、免疫印迹和等电聚焦。
在四名受影响成员中鉴定出一个纯合的28个核苷酸的移码缺失，该缺失在第1外显子中引入了一个提前终止密码子。我们进一步证实了无义介导的信使RNA（mRNA）降解途径明显的转录逃避。实时PCR显示，与野生型相比，突变体的mRNA表达更高。蛋白质免疫印迹和等电聚焦鉴定出在患者原代细胞中表达的截短但稳定的突变型PTRHD1蛋白。
我们提供了进一步的证据，表明PTRHD1突变与伴有痉挛和帕金森症的常染色体隐性遗传性儿童期智力残疾有关。
