title: MECP2 and CDKL5 gene mutation analysis in Chinese patients with Rett syndrome.
abstract: Rett syndrome (RTT) is a progressive neurodevelopmental disorder that is caused by mutations in the X-linked methyl-CpG-binding protein2 (MECP2) gene. In this study, the MECP2 sequences in 121 unrelated Chinese patients with classical or atypical RTT were screened for deletions and mutations. In all, we identified 45 different MECP2 mutations in 102 of these RTT patients. The p. T158M mutation (15.7%) was the most common, followed in order of frequency by p. R168X (11.8%), p. R133C (6.9%), p. R270X (6.9%), p. G269fs (6.9%), p. R255X (4.9%), and p. R306C (3.9%). In addition, we identified five novel MECP2 mutations: three missense (p. K305E, p. V122M, p. A358T), one insertion (c.45-46insGGAGGA), and one 22 bp deletion (c.881-902del22). Large deletions represented 10.5% of all identified MECP2 mutations. Conversely, mutations in exon 1 appeared to be rare (0.9%). The remaining cases without MECP2 mutations were screened for the cyclin-dependent kinase-like 5 (CDKL5) gene using denaturing high-performance liquid chromatography (DHPLC). One synonymous mutation (p. I72I) was found in exon 5, suggesting that CDKL5 is a rare cause of RTT. The overall MECP2 mutation detection rate for this patient series was 84.3:87.9% in 107 classical RTT cases and 57.1% in 14 atypical RTT cases. Moreover, there were two patients with homozygous mutations and normal female karyotypes. However, we did not pinpoint a significant relationship between genotype and phenotype in these cases.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No.1 of Xi An Men Street, Xi Cheng District, Beijing, 100034, People's Republic of China.
authors.forename: Mei-Rong
authors.initials: MR
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No.1 of Xi An Men Street, Xi Cheng District, Beijing, 100034, People's Republic of China. panmuren@yahoo.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No.1 of Xi An Men Street, Xi Cheng District, Beijing, 100034, People's Republic of China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Bao
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No.1 of Xi An Men Street, Xi Cheng District, Beijing, 100034, People's Republic of China.
authors.forename: Yu-Zhi
authors.initials: YZ
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, No.1 of Xi An Men Street, Xi Cheng District, Beijing, 100034, People's Republic of China.
authors.forename: Xi-Ru
authors.initials: XR
authors.lastname: Wu
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D017353:Gene Deletion; D006801:Humans; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics*
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human