RT Journal Article
SR Electronic
T1 Charcot–Marie–Tooth disease: frequency of genetic subtypes and guidelines for genetic testing
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP 706
OP 710
DO 10.1136/jnnp-2012-302451
VO 83
IS 7
A1 Sinead M Murphy
A1 Matilde Laura
A1 Katherine Fawcett
A1 Amelie Pandraud
A1 Yo-Tsen Liu
A1 Gabrielle L Davidson
A1 Alexander M Rossor
A1 James M Polke
A1 Victoria Castleman
A1 Hadi Manji
A1 Michael P T Lunn
A1 Karen Bull
A1 Gita Ramdharry
A1 Mary Davis
A1 Julian C Blake
A1 Henry Houlden
A1 Mary M Reilly
YR 2012
UL http://jnnp.bmj.com/content/83/7/706.abstract
AB Background Charcot–Marie–Tooth disease (CMT) is a clinically and genetically heterogeneous group of diseases with approximately 45 different causative genes described. The aims of this study were to determine the frequency of different genes in a large cohort of patients with CMT and devise guidelines for genetic testing in practice.Methods The genes known to cause CMT were sequenced in 1607 patients with CMT (425 patients attending an inherited neuropathy clinic and 1182 patients whose DNA was sent to the authors for genetic testing) to determine the proportion of different subtypes in a UK population.Results A molecular diagnosis was achieved in 62.6% of patients with CMT attending the inherited neuropathy clinic; in 80.4% of patients with CMT1 (demyelinating CMT) and in 25.2% of those with CMT2 (axonal CMT). Mutations or rearrangements in PMP22, GJB1, MPZ and MFN2 accounted for over 90% of the molecular diagnoses while mutations in all other genes tested were rare.Conclusion Four commonly available genes account for over 90% of all CMT molecular diagnoses; a diagnostic algorithm is proposed based on these results for use in clinical practice. Any patient with CMT without a mutation in these four genes or with an unusual phenotype should be considered for referral for an expert opinion to maximise the chance of reaching a molecular diagnosis.