CMT1A와 HNPP 신경질환의 진단을 위한 Microsatellite 다중 중합효소연쇄반응 시스템의 개발 = Diagnosis of Neuropathies for CMT1A and HNPP Using the Microsatellite Multiplex PCR System

다국어 초록 (Multilingual Abstract)

Background: Tandem duplication of chromosome 17p11.2-p12 including peripheral myelin protein 22 (PMP22) gene is the most frequent cause of Charcot-Marie-Tooth 1A (CMT1A). Patients carrying one extra copy of PMP22 develop CMT1A, whereas the deletion of the 17p11.2-p12 region causes hereditary neuropathy with the liability to pressure palsies (HNPP). In the present study, we established the genotyping methods of 6 microsatellite markers (D17S921, D17S9B, D17S9A, D17S4A, D17S918 and D17S122) within the 17p11.2-p12 regions by the hexaplex PCR for the genetic diagnosis of CMT1A duplication and HNPP deletion.
Methods: We established polymorphic behavior and genotyping methods of 6 microsatellite markers (D17S921, D17S9B, D17S9A, D17S4A, D17S918 and D17S122) within the duplication region. The 6 markers were amplified by hexaplex PCR reaction and analyzed by an automatic sequencing analyzer and genotyper program.
Results: The genotype distributions of all markers were not significantly deviated from the Hardy-Weinberg equilibrium (P≥0.05). When comparing the control group and CMT1A, HNPP patients group by the distribution of allele, there is no significant difference in the 5 locus except in the 1 locus (D17S921) among HNPP patients. The specificity was more than 99.9%. The sensitivity of each CMT1 and HNPP was 56.3% (40/71 pedigrees) and 72.1% (31/43 HNPP pedigrees), respectively.
Conclusions: The error rate for the system may be less than 0.001. According to this study, it is possible to have rapid and exact genetic diagnosis of both CMT1A and HNPP, which may be helpful for the development of personalized therapy according to genetic defects.

참고문헌 (Reference)

• 1 "Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease(CMT-1A)" 9 : 1533-1537, 2003
• 2 "The 1.4-Mb CMT1A duplication/HNPP deletion genomic region reveals unique genome architectural features and provides insights into the recent evolution of new genes" 11 : 1018-1033, 2001
• 3 "Rapid screening of myelin genes in CMT1 patients by SSCP analysis:identification of new mutations and polymorphisms in the P0 gene" 94 : 653-657, 1994
• 4 "Prevalence of the 1.5-Mb 17p deletion in families with hereditary neuropathy with liability to pressure palsies" 36 : 650-655, 1994
• 5 "Polymorphic short tandem repeats for diagnosis of the Charcot-Marie-Tooth IA duplication" 47 : 829-837, 2001
• 6 "Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion" 46 : 1133-1137, 1996
• 7 "PCR-based strategy for the diagnosis of hereditary neuropathy with liability to pressure palsies and Charcot- Marie-Tooth disease type 1A" 50 : 760-763, 1998
• 8 "New polymorphic short tandem repeats for PCR-based Charcot-Marie-Tooth disease type 1A duplication diagnosis" 47 : 838-843, 2001
• 9 "New allele of probe D17S61 present in the Charcot-Marie-Tooth 1A duplication" 46 : 380-381, 1994
• 10 "Nerve conduction study of hereditary neuropathy with liability to pressure palsies" 2 13-18, 1999
• 11 "Mutational analysis of PMP22 EGR2 and NEFL in Korean Charcot-Marie-Tooth neuropathy patients" 2004
• 12 "Molecular cell biology of Charcot- Marie-Tooth disease" 1-15, 2002
• 13 "Improved testing for CMT1A and HNPP using multiplex ligation-dependent probe amplification comparison with the interphase FISH method" 164-171, 2004
• 14 "Hereditary neuropathy with liability to pressure palsies.Electrophysiological and histopathological aspects" 95 : 777-794, 1972
• 15 "Hereditary neuropathy with liability to pressure palsies" 176-184, jneurolsci1993
• 16 "Hereditary neuralgic amyotrophy and hereditahy neuropathy with liability to pressure palsies:two distinct clinical,electrophysiologic,and genetic entities" 44 : 2250-2252, 1994
• 17 "From the syndrome of Charcot,Marie and Tooth to disorders of peripheral myelin proteins" 118 : 809-818, 1995
• 18 "Disease mechanisms in inherited neuropathies" 714-726, 2003
• 19 "Deletion in the CMT1A locus on chromosome 17p11.2 in hereditary neuropathy with liability to pressure palsies" 35 : 704-708, 1994
• 20 "DNA duplication associated with Charcot- Marie-Tooth disease type 1A" 66 : 219-232, 1991
• 21 "DNA deletion associated with hereditary neuropathy with liability to pressure palsies" 72 : 143-151, 1993
• 22 "Charcot-Marie-Tooth syndrome" 50 : 1180-1184, 1993
• 23 "Charcot-Marie-Tooth neuropathies:from clinical description to molecular genetics" 18 : 267-275, 1995
• 24 "Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease" 10 : 396-401, 2004
• 25 "Analysis of the CMT1A- REP repeat:mapping crossover breakpoints in CMT1A and HNPP" 4 : 2327-2334, 1995