Genetic study of inherited peripheral neuropathy disease (Charcot–Marie Tooth) disease

Background Charcot-Marie-Tooth disease (CMT) is the most common hereditary neuromuscular disorder. Charcot-Marie-Tooth disease can be caused by mutations in many different genes. These genes provide instructions for making proteins involved in the functioning of the peripheral nerves of the feet, legs, and hands. Peripheral myelin protein 22 (PMP22) related neuropathies account for over 50% of inherited peripheral neuropathies. Agene copy variation results in CMT1A (duplication of 17p11.2.p12) and hereditary neuropathy with liability to pressure palsies (HNPP; single deletion). Point mutation comprise both phenotypes. The underlying pathological mechanisms are incompletely understood and biallilic mutations of PMP22 are very rare. Objective To study clinical characteristics of a cohort of Egyptian patients with CMT; frequency of PMP22 gene duplication and deletion by MLPA and molecular diagnosis. Methodology We applied our study on 97 Egyptian patients from 70 unrelated families with suspected CMT disease, patients were referred from different provinces to Ain Shams neuromuscular outpatient clinic. After an informed and written consent, all patients were examined neurologically and systemically. Diagnosis was based on clinical symptoms, electromyography and genetic study. Results Clinical classification of our patients revealed high incidence rate of AR CMT type patients (43.3%) and sporadic cases (39.3%), while AD CMT type represents (17.5%), the cause of the high rate of negative family history of same disease affection may be for many reasons mild subclinical expression in other family members, autosomal recessive inheritance, or a de novo heterozygous pathogenic variant in a gene associated with autosomal dominant inheritance. Neurophysiological classification according to median NCV shows that 53 patients (51.5%) have axonal sensory-motor affection with median NCV <38 m/s, 26 patients (26.8%) have demyelinating CMT type, and 19 patients (19.6%) have intermediate type (mixed axonal and demyelinating affection with median NCV range between 35 m/s to 45 m/s. Thus the commonest form is CMT 2 (axonal AR type) followed by CMT 4 (demyelinating AR type) with lower incidence of CMT 1 (demyelinating AD type). Conclusion from our study we concluded that (AR CMT type) is not uncommon in Egypt because of the high prevalence of consanguinity, and that PMP22 duplication is not a common cause of Egyptian inherited neuropathy disease.