Four novel mutations of the myelin protein zero gene presenting as a mild and late-onset polyneuropathy

Abstract

Inherited neuropathies caused by mutations of the major structural protein of peripheral myelin, myelin protein zero (MPZ), contribute to 5% of all cases of Charcot-Marie-Tooth disease (CMT). They can be divided into an early-onset neuropathy with symptoms prior to the stage of walking, and a late-onset neuropathy with symptoms at the age of 40 and older. In this study, five patients with four novel MPZ mutations were identified by molecular genetic testing which presented as mild and late-onset neuropathies. We recommend testing for MPZ mutations in patients with a late-onset neuropathy, as late-onset inherited neuropathies might be more frequent than previously thought.

Early-onset CMT1B due to the MPZ mutation c.320A>T associated with collateral inclusion body myopathy and Deafness

“…Since neuropathy was of the demyelinating type and since the transmission followed an autosomal dominant trait-of-inheritance, the presented case was diagnosed as CMT1B, which has been repeatedly reported in the literature [16,17,18,19]. CMT1B patients present either with severe early-onset (prior to stage of walking) demyelinating neuropathy or with late-onset (>40y of age), demyelinating sensorimotor polyneuropathy with prominent axonal loss [2,17]. There is lower limb-predominance of weakness, wasting, and sensory disturbances, and foot deformity but hardly pupil anomalies, or deafness in early-onset CMT1B.…”

“…MPZmutations may not only manifest as sensorimotor neuropathy but also as multiple sclerosislike phenotype [10], with Adie's pupil [4] or other abnormal pupillary reaction [14], autonomic dysfunction [24], recurrent nerve compression [1], with isolated spinal root hypertrophy [25], respiratory failure [24], CK-elevation [4], or impaired hearing [4,10,11,12]. MPZ mutations contribute to 5% of the CMT cases [2]. MPZ mutations most frequently manifest as CMT1B, but only rarely as CMT2I/J, Dejerine-Sottas syndrome.…”

“…Mutations in the myelin protein zero (MPZ) gene cause hereditary, autosomal dominant demyelinating sensorimotor polyneuropathy Charcot-Marie-Tooth (CMT) 1B [1], late-onset, mixed demyelinating and axonal polyneuropathy [2,3]. late-onset autosomal dominant, axonal sensorimotor polyneuropathy CMT 2I/J [3,4], early-onset Dejerine-Sottas syndrome [5], or congenital hypomyelinating polyneuropathy [6,7,8,9].…”

Impaired Mitochondrial Mobility in Charcot-Marie-Tooth Disease

“…( Avila et al, 2010;Bergamin et al, 2014;Bienfait et al, 2006;Bissar-Tadmouri et al, 1999;Blanquet-Grossard et al, 1996;Brozková, Mazanec, Haberlová, Sakmaryová, & Seeman, 2010;Chavada, Rao, Martindale, & Hadjivassiliou, 2012;Choi et al, 2011;De Jonghe et al, 1999;Dohrn et al, 2017;Gallardo et al, 2009;Hayasaka et al, 1993;He et al, 2018;Høyer et al, 2014;Høyer, Braathen, Eek, Skjelbred, & Russell, 2011;Kleffner, Schirmacher, Gess, Boentert, & Young, 2010;Kochański et al, 2004;Kurihara et al, 2004;Lagueny et al, 1999;Latour et al, 1995;Laurà et al, 2007;Leal et al, 2014;Lee et al, 2008;Maeda et al, 2012;Marttila et al, 2012;Mazzeo et al, 2008;Milley et al, 2018;Nelis et al, 1994;Pham-Dinh et al, 1993;Quattrini et al, 1999;Roa et al, 1996;Rosberg, Alvarez, Krarup, & Moldovan, 2013;Rudnik-Schöneborn et al, 2016;Sabet et al, 2006;Sanmaneechai et al, 2015;…”