title: Novel POLG mutation in a patient with sensory ataxia, neuropathy, ophthalmoparesis and stroke.
abstract: BACKGROUND
  Clinical diagnosis of POLG-related disorders can be challenging because the phenotypic spectrums are heterogeneous which can mimic different types of mitochondrial disorders.
  
  
  METHODS
  We report a case of POLG-related disorder in an 18y Chinese girl who had been diagnosed as MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) for the past 8y. She first presented at 10y with sudden onset of headache, repeated focal seizures and visual loss, complicated with residual sensory and motor neuropathy, ophthalmoparesis and cortical blindness. MRI brain showed extensive cytotoxic edema and ischemia in bilateral parietal-occipital lobes. Mutation analysis for common point mutations in the mitochondrial DNA and muscle biopsy was negative. She was referred to us for mitochondrial whole genome analysis. However, no pathogenic variants can be determined. We initiated further genetic analysis for POLG which confirmed compound heterozygous mutations NM_002693.2:c.925C>T (p.Arg309Cys) and a novel mutation c.2244G>T (p.Trp748Cys). Both were determined to be pathogenic using in silico analysis.
  
  
  CONCLUSIONS
  The novel mutation contributes to the expanding spectrum of disease-causing mutations. A definitive diagnosis can benefit our patient and also the relatives by avoiding sodium valproate induced liver toxicity in POLG patients and also the heterozygotes.
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China. Electronic address: ching-wanlam@pathology.hku.hk.
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.affiliation: Department of Pathology, The University of Hong Kong, Hong Kong, China.
authors.forename: Chun-Yiu
authors.initials: CY
authors.lastname: Law
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Wai-Kwan
authors.initials: WK
authors.lastname: Siu
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong, China.
authors.forename: Cheuk-Wing
authors.initials: CW
authors.lastname: Fung
authors.affiliation: Department of Pediatrics, Tseung Kwan O Hospital, Hong Kong, China.
authors.forename: Man-Mut
authors.initials: MM
authors.lastname: Yau
authors.affiliation: Department of Pediatrics, Tseung Kwan O Hospital, Hong Kong, China.
authors.forename: Kwai-Fun
authors.initials: KF
authors.lastname: Huen
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Hencher Han-Chih
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Princess Margaret Hospital, Hong Kong, China.
authors.forename: Chloe Miu
authors.initials: CM
authors.lastname: Mak
mesh_terms: D000293:Adolescent; D001259:Ataxia / Q000150:complications* / Q000235:genetics*; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009886:Ophthalmoplegia / Q000150:complications / Q000235:genetics*; D011115:Polyneuropathies / Q000150:complications* / Q000235:genetics*; D020521:Stroke / Q000150:complications* / Q000235:genetics*
chemical_list: D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: Neuropathy; Ophthalmoparesis; POLG; Sensory ataxia; Stroke