Duchenne/Becker 근이영양증에서의 임상적, 면역조직학적 및 유전학적 소견 = The Clinical Features, Immunostaining and Genetic Study in Duchenne/Becker Muscular Dystrophy

국문 초록 (Abstract)

목 적:본원에서 Duchenne 및 Becker 근이영양증(DMD/BMD)으로 진단된 환자에서 임상양상과 multiplex PCR 또는 MLPA를 이용한 디스트로핀 유전자 결손, 면역조직화학 염색에 의한 디스트로핀 발현을 조사하여 각 임상형의 특징과 각 검사의 진단적 유용성에 대해 고찰해 보았다.
방 법:1989년 6월부터 2008년 12월까지 서울아산병원에서 진단시 혈청 Creatinine Kinase(CK) 증가가 있고 근육질환의 임상소견을 보이는 환자에서 조직학적 소견 또는 디스트로핀 유전자 검사소견이 DMD/BMD에 부합되는 93명을 대상으로 의무기록을 후향적으로 분석하였다. 성별, 나이, 첫 임상증상의 종류와 발병 연령, 진단시 Gower sign 유무, 가족력, 진단시 혈청 CK 수치, 근전도 및 신경전달속도검사, 대퇴근의 근육생검 및 면역조직학적 검사, 말초혈액을 이용한 디스트로핀 유전자 검사(multiplex PCR 또는 MLPA)를 조사하였다. 또한 frame 유지여부와 임상표현형의 일치율을 구해 보았다.
결과:DMD 58명, BMD 13명, 비분류군(unclassified) 19명, DMD/BMD carrier 3명이었다. 증상이 처음 발견된 연령은 평균 4.7±3.2세(1-17세)였고 첫 증상은 보행장애가 46명(49%)으로 가장 많았고 간효소 상승이 우연히 발견된 경우가 35명(37 %)으로 두번째로 많았다. 진단시 혈청 CK는 평균 14,758±11,792(633-6,1349) IU/L이었고 DMD에서는 18,402±12,117(633-61,349) IU/L, BMD에서는 6,675±6,414(814-17,898) IU/L, unclssified에서는 11,103±9,032(2,623-39,549)IU/L, PMD carrier는 1,281±637(718-1,974),IU/L이었다. 근육 생검을 한 75명중 clone 13H6(N-terminus)를 사용하여 DMD 48명과 BMD 10명에서 면역조직화학염색을 시행하였는데 DMD에서는 48명 모두 디스트로핀이 발현되지 않았으며 BMD에서는 10명 모두 불완전/부분적으로 발현되었다. Multiplex PCR을 시행한 54명중 28명(51%)에서 결손이 발견되었고 MLPA를 시행한 14명 중 13명(92%)에서 결손이 발견되었고 이중 2명은 이형접합결손이었다. Frame 유지여부와 임상표현형의 일치율은 95%를 보였다.
결론:multiplex PCR를 시행한 10명의 환자와 MLPA를 시행한 11명의 환자를 대상으로 frame 유지여부와 임상표현형과의 일치율을 구해보았는데 일치율은 95%로 높았다. 대상군이 적어 추가적인 연구가 필요할 것으로 보이지만 MLPA를 통해 in frame과 out of frame을 결정한 후 DMD/BMD를 예상하는 것은 근육생검을 시행하지 않는 환자에 있어서는 임상적으로 유용하겠다. 또한 MLPA를 통한 carrier의 진단이 유전상담에 있어 큰 도움이 되겠다.

다국어 초록 (Multilingual Abstract)

Purpose:This retrospective study was designed to know the relation between clinical features, genetics, and immunostaining findings among children with Duchenne muscular dystrophy (DMD)/Becker muscular dystrophy (BMD) and the validity of the diagnostic tools for muscular dystrophy.
Methods:The medical records and computerized databases of 93 patients diagnosed with DMD/BMD from June 1989 to December 2008 were reviewed retrospectively. Demographic characteristics including clinical features, serum creatinine kinase(CK) level, electromyogram(EMG) and nerve conduction velocity(NCV), muscle biopsy, immunochemical staining for dystrophin, and the deletion of dystrophin gene were analyzed. We calculate the concordance rate between type of frame (in or out of frame) and phenotype.
Results:58(62%) children were diagnosed with DMD, 13(14%) BMD, 19(20%) unclassified dystrophy, and 3(3%) DMD/BMD carriers. The mean age of symptom onset was 5.0±3.5 years(range, 1-17). 46(49%) children presented gait disturbance and 35(37%) elevation of liver enzymes. The mean value of serum CK enzyme was 14,758±11,792 IU/L (range, 633-61,349). There was no dystrophin in the immunochemical stain among 48 DMD children and at least partial or incomplete dystrophin among 10 BMD children. 28/54(51%) children had dystrophin gene deletion in multiplex PCR and 13/14(92%) in Multiplex Ligation-dependent Probe Amplification(MLPA). The loss of heterozygosity was shown in 2 children by MLPA. The overall concordance rate between type of frame(in or out of frame) and phenotype was 95% in this study.
Conclusion:Despite of small population, this finding indicates that the determination of type of frame (in or out of frame) by MLPA may be helpful in differential diagnosis of DMD/BMD. In addition, we surmise that the detection of carrier by MLPA is helpful in genetic counseling.

목차 (Table of Contents)

• 서론
• 대상 및 방법
• 결과
• 고찰
• References
• 초록

참고문헌 (Reference)

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