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<p>Essential tremor (ET) is a common movement disorder, but its pathophysiologic mechanisms remain elusive. So far, a few genes/loci have been identified, but because of genetic heterogeneity, the genetic etiology of ET is still one of the main challenges. In this study, we report an autosomal dominant ET Chinese pedigree in which the patients presented with involuntary tremor of the head or upper limbs, with a slow progression of symptoms, no difficulty in starting and turning, no slow walking, no other significant findings were noted on neurological examination. A heterozygous missense mutation (c.158G &gt; A, p.G53D) in <i>PINK1</i> (PTEN-induced kinase 1) was identified by whole-exome sequencing of four affected individuals from this ET family. Confirmed by Sanger sequencing, we find that this <i>PINK1</i> missense variant co-segregate with ET phenotypes in this pedigree with all the affected subjects, showing clear genotype-phenotype correlation. In addition, the new missense mutation was functionally analyzed by western blotting and mitochondrial membrane potential assay after cell transfection. It was found that <i>PINK1</i> may play a protective role for cells, whereas the c.158G &gt; A (p.G53D) missense mutation leads to a loss of cellular protection, thereby increasing cellular sensitivity to stress. Thus, this study provides a heterozygous missense mutation in <i>PINK1</i> potentially associated with ET.</p>

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A heterozygous variation of PINK1 is potentially associated with essential tremor in a Chinese family

  • 期刊论文

  • 发表日期：

    2025年5月26日

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  • Bin Wang,
  • Bin Wei,
  • Likui Lu,
  • Sha Liu,
  • Wei Ge,
  • Miao Sun

摘要

Essential tremor (ET) is a common movement disorder, but its pathophysiologic mechanisms remain elusive. So far, a few genes/loci have been identified, but because of genetic heterogeneity, the genetic etiology of ET is still one of the main challenges. In this study, we report an autosomal dominant ET Chinese pedigree in which the patients presented with involuntary tremor of the head or upper limbs, with a slow progression of symptoms, no difficulty in starting and turning, no slow walking, no other significant findings were noted on neurological examination. A heterozygous missense mutation (c.158G > A, p.G53D) in PINK1 (PTEN-induced kinase 1) was identified by whole-exome sequencing of four affected individuals from this ET family. Confirmed by Sanger sequencing, we find that this PINK1 missense variant co-segregate with ET phenotypes in this pedigree with all the affected subjects, showing clear genotype-phenotype correlation. In addition, the new missense mutation was functionally analyzed by western blotting and mitochondrial membrane potential assay after cell transfection. It was found that PINK1 may play a protective role for cells, whereas the c.158G > A (p.G53D) missense mutation leads to a loss of cellular protection, thereby increasing cellular sensitivity to stress. Thus, this study provides a heterozygous missense mutation in PINK1 potentially associated with ET.