title: Follow-up study of 25 Chinese children with PLA2G6-associated neurodegeneration.
abstract: BACKGROUND
  To perform a follow-up of 25 Chinese children with gene-confirmed PLA2G6-associated neurodegeneration (PLAN).
  
  
  METHODS
  We recruited patients with infantile neuroaxonal dystrophy (INAD) according to the criteria proposed by Nardocci et al. Follow-up was conducted from 7 months to 8 years after the first visit. The PLA2G6 gene was sequenced, and copy number variation (CNV) was detected in patients with only one mutant allele and in mutation-negative patients. Patients with late-onset PLAN until 2012 were reviewed.
  
  
  RESULTS
  All patients with INAD exhibited rapid decline in motor and mental function, consistent with previous reports from other populations. Epileptic seizures occurred in 16.7%. One teenager with late-onset PLAN was diagnosed and followed up. The age of disease onset in published late-onset PLAN ranged between 18 months and 37 years. Initial presentations included gait instability (79.0%), mood/behavior changes (10.5%), dysarthria (5.26%) and cognitive deterioration (5.3%). Compared with INAD, cerebellar atrophy (42.1%) was less frequent in the late-onset cases, with cerebral atrophy more common (71.4%). Brain iron accumulation was seen in 52.6%. PLA2G6 mutations were identified by DNA sequencing in 92.3% of clinically diagnosed INAD cases and in the late-onset case. Twenty-seven different mutations were found, of which 13 were novel. No CNVs were detected. Maternal uniparental disomy was confirmed in one INAD case.
  
  
  CONCLUSIONS
  This is the largest report on PLAN in the Chinese population. We suggest that PLA2G6 should be screened in any patient exhibiting progressive gait disturbance, bradykinesia, dysarthria, tremors, mood/behavior changes or cognitive decline, especially when associated with cerebellar atrophy and/or iron accumulation and/or cerebral atrophy.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Gao
authors.forename: Y
authors.initials: Y
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Xiong
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: X
authors.initials: X
authors.lastname: Bao
authors.forename: J
authors.initials: J
authors.lastname: Xiao
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
mesh_terms: D044466:Asian People / Q000235:genetics*; D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006801:Humans; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019150:Neuroaxonal Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059906:Neuroimaging; D010641:Phenotype
chemical_list: D007501:Iron; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human