Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies

BMC Medical Genetics

Øivind Nilssen³  Svein I Mellgren²  Bjørn Nygård¹  Helene Hjellnes¹  Toril Fagerheim¹  Rune Østern³ 

[1]Department of Medical Genetics, University Hospital of North-Norway, Tromsø NO9038, Norway

[2]Department of Neurology, University Hospital of North-Norway, Tromsø NO9038, Norway

[3]Department of Clinical Medicine, Neuromuscular Research Group, University of Tromsø, Tromsø NO9037, Norway

关键词: Guidelines;    Clinical neurophysiology;    Mutation analysis;    Neuromuscular diseases;    Genetic and inherited disorders;    Charcot-Marie-Tooth;   

Others  :  1122635
DOI  :  10.1186/1471-2350-14-94

 received in 2013-04-27, accepted in 2013-09-17,  发布年份 2013

【 摘 要 】

Background

Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions for clinical assessment. However, in a diagnostic laboratory setting relying on external test requisitions and patient samples, such conditions are not always met. Our objective was therefore to perform a retrospective evaluation of the data given in laboratory request forms and to assess their quality and applicability with regard to the recommended algorithms for CMT diagnostics. As we are the main test centre for CMT in Norway our results also provide an overview of the spectrum of gene defects in the Norwegian CMT population.

Methods

Genetic testing was performed according to polyneuropathy type; demyelinating/mixed: PMP22 duplication, MPZ, EGR2, LITAF, NEFL, PMP22, GJB1, axonal: MFN2, MPZ, NEFL, and GJB1.

Results

Diagnostic testing of index patients was requested in 435 of the 549 cases. Seventy-two (16.6%) positive molecular genetic findings were made. The majority (94.6%) of mutation positive cases showed disease onset before 50 years of age. PMP22 (duplication), MPZ, GJB1 and MFN2 mutations constituted 95.8% of the positive findings. Within the nerve conduction study groups, mutation detection rates were; demyelinating 33.8%; mixed 29.0%; axonal 8.8%; unspecified 16.5%.

Conclusion

We suggest a simplified algorithm intended for referral centres, dealing with DNA/blood samples, which involves the assessment of age at onset and neurophysiological data followed by testing of four genes; PMP22 (duplication), MPZ, GJB1 and MFN2. Patients negative for mutations in those four genes should be subjected to evaluation at an interdisciplinary inherited neuropathy clinic with the capacity for extended molecular genetic analysis by next generation sequencing.

【 授权许可】

   
2013 Østern et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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