Charcot-Marie-Tooth Disease, molecular epidemiology in Northern Ostrobothnia

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Oulu University Hospital, Auditorium 8

Topic of the dissertation

Charcot-Marie-Tooth Disease, molecular epidemiology in Northern Ostrobothnia

Doctoral candidate

Licentiate of Medicine Maria Lehtilahti

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, The Research Unit of Clinical Neuroscience

Subject of study

Neurology

Opponent

Professor Seppo Soinila, University of Turku

Custos

Professor Kari Majamaa, University of Oulu

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Hereditary Neuropathies

Charcot-Marie-Tooth (CMT) disease is probably the most common inherited neuromuscular disorder in the world. The most common symptoms and signs in CMT patients are difficulties in walking, reduced or absent tendon reflexes, foot deformities, distal predominance of limb muscle weakness and sensory loss. Pathogenic variants in over 100 genes are known to cause CMT.
The aim of this study was to investigate the molecular epidemiology of CMT in Northern Ostrobothnia, and to evaluate patients with pathogenic variants in GDAP1 and MPZ genes.
We found 107 patients with CMT, suggesting a prevalence 34.6/100,000 in Northern Ostrobothnia. The dominantly inherited pathogenic variant p.His123Arg in GDAP1 was found in 31.5% of the patients, and PMP22 duplication in 16.9% of the patients. Twentythree patients with p.His123Arg in GDAP1 were examined clinically and electrodiagnostically. A remarkable number of patients had proximal muscle weakness of the legs and asymmetry of symptoms and findings. In two families we found a novel variant, p.His106Arg, in the MPZ gene. It causes dominantly inherited, late-onset, relatively mild polyneuropathy.
Prevalence of CMT in Northern Ostrobothnia appears to be two-fold higher than the average in European populations. One reason could be the high portion of patients with the pathogenic variant in GDAP1-gene. P.His123Arg in GDAP1-gene may be the most common single pathogenic variant in patients with CMT in Finland, and a cluster of the variant was found in Northern Ostrobothnia. Prevalence of this variant in other parts of Finland is not known.
Last updated: 20.5.2022