Diagnostic mutational analysis of MECP2 in Korean patients with Rett syndrome.
- Author:
In Joo KIM
1
;
Yeon Joo KIM
;
Byeong Hee SON
;
Sang Ook NAM
;
Hoon Chul KANG
;
Heung Dong KIM
;
Mi Ae YOO
;
Ook Hwan CHOI
;
Cheol Min KIM
Author Information
1. Department of Biochemistry, College of Medicine, Pusan National University, Busan 602-739, Korea. kimcm@pusan.ac.kr
- Publication Type:Original Article
- Keywords:
DNA mutational analysis;
diagnosis;
MECP2 protein;
human;
polymorphism;
restriction fragment length;
Rett syndrome
- MeSH:
Rett Syndrome/diagnosis/*genetics;
Polymorphism, Single Nucleotide;
Polymorphism, Restriction Fragment Length;
Polymerase Chain Reaction;
*Mutation;
Molecular Sequence Data;
Methyl-CpG-Binding Protein 2/*genetics;
Male;
Korea;
Humans;
Female;
DNA Mutational Analysis;
Base Sequence
- From:Experimental & Molecular Medicine
2006;38(2):119-125
- CountryRepublic of Korea
- Language:English
-
Abstract:
Rett syndrome (RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000- 15,000 female births worldwide. The disease-causing gene has been identified as MECP2 (methyl- CpG-binding protein 2). In this study, we performed diagnostic mutational analysis of the MECP2 gene in RTT patients. Four exons and a putative promoter of the MECP2 gene were analyzed from the peripheral blood of 43 Korean patients with Rett syndrome by PCR-RFLP and direct sequencing. Mutations were detected in the MECP2 gene in approximately 60.5% of patients (26 cases/43 cases). The mutations consisted of 14 different types, including 9 missense mutations, 4 nonsense mutations and 1 frameshift mutation. Of these, three mutations (G161E, T311M, p385fsX409) were newly identified and were determined to be disease-causing mutations by PCR- RFLP and direct sequencing analysis. Most of the mutations were located within MBD (42.3%) and TRD (50%). T158M, R270X, and R306C mutations were identified at a high frequency. Additionally, an intronic SNP (IVS3+23C>G) was newly identified in three of the patients. IVS3+23C>G may be a disease-related and Korea-specific SNP for RTT. L100V and A201V are apparently disease-causing mutations in Korean RTT, contrary to previous studies. Disease-causing mutations and polymorphisms are important tools for diagnosing RTT in Koreans. The experimental procedures used in this study should be considered for clinical molecular biologic diagnosis.
