Mutational Analysis of MECP2 Gene in 34 Rett Syndrome

Park, Sang Jo; Hwang, Tae Gyu; Son, Byeong Hee; Kim, Chul Min

Original Article

Journal of the Korean Pediatric Society 2002;45(10):1263-1272.
Published online October 15, 2002.

Mutational Analysis of MECP2 Gene in 34 Rett Syndrome

Sang Jo Park¹, Tae Gyu Hwang¹, Byeong Hee Son², Chul Min Kim³

¹Department of Pediatrics, College of Medicine, Inje University, Busan Paik Hospital, Busan, Korea
²Department of Pediatrics, St. Benedict Hospita, Busan, Korea
³Department of Biochemistry, College of Medicine, Busan National University, Busan, Korea

Rett 증후군 34례의 MECP2 유전자 변이에 관한 연구

박상조^¹^, 황태규^¹^, 손병희^²^, 김철민^³

^¹인제대학교 의과대학 부산백병원 소아과
^²성분도병원 소아과
^³부산대학교 의과대학 생화학교실

Correspondence:
Byeong Hee Son, Email: pedson@medigate.net

Abstract

Purpose
: Rett syndrome(RTT) is an X-linked dominant neurodevelopmental disorder affecting 1 per 10,000-15,000 female births worldwide. It was initially described by Andreas Rett in 1966. RTT involves developmental regression characterized stereotypic hand movements, tremors, gait apraxia, seizures, deceleration of head growth after the age of 6-18 months. The disease-causing gene was identified as MECP2 on chromosome Xq28. We carried out mutational analysis of MECP2 genes in RTT patients.
Methods
: Whole blood(5 cc) of 34 sporadic RTT patients was collected in EDTA-anticoagulated tubes. Genomic DNA was extracted from peripheral blood using the E.Z.N.A. blood DNA kit. Four exons of the MECP2 gene were amplified by PCR in 34 Korean with RTT. We carried out PCR divided the exon three into two parts and the exon four into five parts. Primer sequences designed by Amir et al. in 1999 were almost used(AF030876). Sequencing primers used were the same as PCR. DNA sequencing reactions were performed using an ABI 377 DNA sequencer and ABI PRISM dye terminator cycle sequencing reaction kit(Perkin-elmer). The results were compared with the normal DNA sequence(X99686). To confirm the change of sequence on novel mutations, RFLP analysis was performed.
Results
: The MECP2 mutations were detected in 23(67.6%) of the 34 patients. The mutations consisted of 12 different types including nine missense and three nonsense mutations. Of these, three (L100V, G161E and T311M) mutations were newly identified. Most of the mutations discovered are located within MBD(39.1%) and TRD(39.1%). In this study, three(T158M, R270X, R306C) mutations were identified high frequency.
Conclusion
: MECP2 gene was also an important cause of Korean RTT patients. MECP2 gene study is an important tool for diagnosis of Korean RTT patients.

Key Words: Rett syndrome, MECP2