Complete Loss of Myelin protein zero (MPZ) in a patient with a late onset Charcot-Marie-Tooth (CMT)

AbstractCharcot-Marie-Tooth (CMT) comprises a group of hereditary neuropathies with clinical, epidemiological, and molecular heterogeneity in which variants in more than 80 different genes have been reported. One of the important genes which cause 5% of all CMT cases is Myelin protein zero (P0,MPZ). Variants in this gene have been reported in association with different forms of CMT including classical CMT1, severe DSS (CMT3B), DI-CMT, CMT2I and CMT2J with autosomal dominant (AD) inheritance. To our knowledge,MPZ variants have not been described in autosomal recessive (AR) form of CMT in previous studies. Moreover, its complete deletion has not been reported in human. Here, we described clinical characteristics of a patient with CMT symptoms who demonstrated manifestations of the disease late in his life. We performed exome sequencing for identifying CMT subtype and its associated gene, and follow that co-segregation analysis has been done to characterize inheritance pattern of the disorder. Through using exome sequencing, we identified a novel 4074  bp homozygote deletion which encompasses all 6 exons of theMPZ gene in this patient. After identifying the alteration, variant confirmation and co-segregation analysis have been performed by using specific primers. Our result revealed that the patient ’s parents were heterozygous for the alteration and they did not show any symptoms of CMT. Although mostMPZ variants have been described with early onset CMT with AD pattern of in...
Source: Metabolic Brain Disease - Category: Neurology Source Type: research