Molecular diagnosis of inheritable neuromuscular disorders. Part II: Application of genetic testing in neuromuscular disease

Abstract

Molecular genetic advances have led to refinements in the classification of inherited neuromuscular disease, and to methods of molecular testing useful for diagnosis and management of selected patients. Testing should be performed as targeted studies, sometimes sequentially, but not as wasteful panels of multiple genetic tests performed simultaneously. Accurate diagnosis through molecular testing is available for the vast majority of patients with inherited neuropathies, resulting from mutations in three genes (PMP22, MPZ, and GJB1); the most common types of muscular dystrophies (Duchenne and Becker, facioscapulohumeral, and myotonic dystrophies); the inherited motor neuron disorders (spinal muscular atrophy, Kennedy's disease, and SOD1 related amyotrophic lateral sclerosis); and many other neuromuscular disorders. The role of potential multiple genetic influences on the development of acquired neuromuscular diseases is an increasingly active area of research.

Dysmyelinating and demyelinating Charcot–Marie–Tooth disease associated with two myelin protein zero gene mutations

“…This ratio of MPZ gene mutations within CMT-affected patients corresponds with the MPZ gene mutation frequency within CMT1-affected patients estimated to be in the range from 3 to 11% from reports in the literature (Greenberg and Walsh 2005;Nelis et al 1996).…”

“…The genes mutated in the CMT1 patients (PMP22, MPZ, LITAF, and EGR-2) code for proteins with different cellular functions and locations (Barisic et al 2008). The vast majority of CMT1 patients harbor duplications of the PMP22 gene, with only some patients carrying point mutations within this gene (Greenberg and Walsh 2005). In about 3% patients in which CMT was diagnosed mutations in the Myelin Protein Zero (MPZ) gene have been identified (Greenberg and Walsh 2005).…”

“…The vast majority of CMT1 patients harbor duplications of the PMP22 gene, with only some patients carrying point mutations within this gene (Greenberg and Walsh 2005). In about 3% patients in which CMT was diagnosed mutations in the Myelin Protein Zero (MPZ) gene have been identified (Greenberg and Walsh 2005).…”

Improved diagnostic yield of neuromuscular disorders applying clinical exome sequencing in patients arising from a consanguineous population

“…However, there is another issue to consider, in that it is now much more efficient to use noninvasive genetic tests rather than these ancillary and invasive methods such as muscle or nerve biopsy (29). Due to the high cost of these methods, it is important to have a precise primary diagnosis with the help of ancillary methods.…”

Der Einsatz der Magnetresonanztomographie der Muskulatur bei der Diagnose neuromuskulärer Erkrankungen

“…CCTG-Repeat-Expansionen der myotonen Dystrophie Typ I bzw. Typ II (proximale myotone Myopathie) und bei der Mehrzahl der Betroffenen auch die partiellen Dystrophin-Deletionen der BeckerKiener-Muskeldystrophie [20]. Bei den Gliedergürtel-dystrophien ist wegen der großen Zahl der verschiedenen Genloci die molekulargenetische Testung noch zu komplex, um sie ohne weiteres in der klinischen Routine-diagnostik anwenden zu können.…”