Myelin thickenings in val 102/fs null mutation of MPZ gene

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Myelin thickenings, abnormal myelin foldings and tomacula have been rarely described in CMT1B. In two unrelated patients of different age (patient 1: 29 years old; patient 2: 65 years old) with CMT1B and Val 102/fs null mutation of MPZ gene we performed morphometric analysis, teased fibers and ultrastructural examination of sural nerve. We found: 1) markedly decreased fiber density with prevalent loss of large diameter fibers (patient 1: 4419 fibers/mm2; patient 2: 1326 fibers/mm2); 2) evidence of de‐remyelination; and 3) paranodal and internodal myelin thickenings in virtually all fibers. Patient 1 has myelin thickenings measuring more than 50% of the fiber diameter in 14% of fibers and thickenings greater than 30% in 33% of fibers. Patients 2 presents myelin thickenings measuring more than 50% of fiber diameter in 23% of fibers and thickening greater than 30% in 49% of fibers. When considering the absolute measure of myelin thickenings and their number over 100 internodes, patient 1 presents 150 small myelin thickenings (<8 mm of diameter) whereas patient 2 has 57. The number of globules (8–12 mm of diameter) is 56 in patient 1 and 45 in patient 2. The number of myelin thickenings greater than 12 mm is 33 in patient 1 and 45 in patient 2. Ultrathin sections showed myelin infoldings, outfoldings and uncompacted myelin. CMT1B with a heterozygous null mutation of MPZ gene is characterized by abundant focal myelin thickenings. Similar findings have been described in the P0 deficient heterozygous mice.