title: [Clinical and genetic study of twelve Chinese patients with Alexander disease].
abstract: OBJECTIVE
  To delineate the phenotype and genotype characteristics in 12 Chinese children with Alexander disease (AD), which is helpful for the molecular diagnosis and genetic counseling in China.
  
  
  METHODS
  Clinical diagnosis of AD was based on MRI criteria proposed by van der Knaarp in 2001. Included AD patients were followed up for 0.50 - 3.67 years. Mutations in GFAP were detected by DNA sequencing.
  
  
  RESULTS
  The 12 cases of AD were clinically diagnosed. Age of first visit was 4.87 years (0.75 - 12.00 years), with 3 types of chief complaints: developmental delay in 3, recurrent seizures in 7, unable to walk after falling in 2. Average head circumference was 52.34 cm (44 - 58 cm), which larger than age-matched average by 6.45% (1.80% - 13.95%). On the first visit, scaling according to Gross motor functional classification system (GMFCS) was performed, with GMFCSI in 8, II in 3, V in 1. Mild to severe cognitive dysfunction were found in 8, and seizures in 11 cases. The 12 patients were followed up for 0.50 - 3.67 years, their motor and cognitive function remained stable. Episodic aggravations provoked by fever or falling were observed in 5 cases (41.67%). Heterozygous missense mutations of GFAP were detected in 12 patients. All mutations were de novo; 3 out of 10 mutations identified were novel. R79 and R239 were hot mutations, which was consistent with previous reports. Mutations were located in exon 1 in 8 cases.
  
  
  CONCLUSIONS
  The phenotype in these patients is characterized by slower progression compared with reports from other population and high incidence of seizures. And episodic aggravations provoked by fever or falling were more common. The genotype characteristics are consistent with previous reports. The results of this research expanded the number of patients with Alexander disease found to have GFAP coding mutations in China.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Zang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wu
authors.forename: Jing-min
authors.initials: JM
authors.lastname: Wang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.forename: Yu-wu
authors.initials: YW
authors.lastname: Jiang
authors.forename: Zhi-jie
authors.initials: ZJ
authors.lastname: Gao
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Jiang-xi
authors.initials: JX
authors.lastname: Xiao
authors.forename: Xi-ru
authors.initials: XR
authors.lastname: Wu
mesh_terms: D038261:Alexander Disease / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D020125:Mutation, Missense / Q000235:genetics*; D012640:Seizures / Q000453:epidemiology; D012720:Severity of Illness Index
chemical_list: D005904:Glial Fibrillary Acidic Protein