2. Academic Validation
  3. The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy

The genotypic and phenotypic spectrum of PARS2-related infantile-onset encephalopathy

  • J Hum Genet. 2018 Sep;63(9):971-980. doi: 10.1038/s10038-018-0478-z.
Xiaomeng Yin 1,  Beisha Tang 1 2 3 4 5 6 7,  Xiao Mao 1,  Jinxin Peng 1,  Sheng Zeng 1,  Yaqin Wang 8,  Hong Jiang 1 2 3 4,  Nan Li 9 10
Affiliations

Affiliations

  • 1 Department of Neurology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China.
  • 2 Center for Medical Genetics, School of Life Sciences, Central South University, 410078, Changsha, Hunan, China.
  • 3 National Clinical Research Center for Geriatric Disorders, Central South University, 410078, Changsha, Hunan, China.
  • 4 Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, 410008, Changsha, Hunan, China.
  • 5 Parkinson's Disease Center of Beijing Institute for Brain Disorders, 100069, Beijing, China.
  • 6 Collaborative Innovation Center for Brain Science, 200032, Shanghai, China.
  • 7 Collaborative Innovation Center for Genetics and Development, 200433, Shanghai, China.
  • 8 Department of Health Management, Third Xiangya Hospital, Central South University, 410013, Changsha, China.
  • 9 Department of Neurology, Xiangya Hospital, Central South University, 410008, Changsha, Hunan, China. [email protected].
  • 10 Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, 410008, Changsha, Hunan, China. [email protected].
PMID: 29915213 DOI: 10.1038/s10038-018-0478-z
Abstract

Mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are a family of enzymes that play critical roles in protein biosynthesis. Mutations in mt-aaRSs are associated with various diseases. As a member of the mt-aaRS family, PARS2 encoding prolyl-tRNA synthetase 2 was recently shown to be associated with Alpers syndrome and certain infantile-onset neurodegenerative disorders in four patients. Here, we present two patients in a pedigree with early developmental delay, epileptic spasms, delayed myelination combined with cerebellar white matter abnormalities, and progressive cortical atrophy. Whole-exome sequencing revealed pathogenic compound heterozygous variants [c.283 G > A (p.95 V > I)] and [c.604 G > C (p.202 R > G)] in PARS2. Nearly all patients had epileptic spasms with early response to treatment, early developmental delay and/or regression followed by generalized hypotonia, postnatal microcephaly, elevated lactate levels, and progressive cerebral atrophy. Our study provides further evidence for validating the role of PARS2 in the pathology of related infantile-onset encephalopathy, contributing to the phenotypic features of this condition, and providing clinical and molecular insight for the diagnosis of this disease entity.

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