Dominant Intermediate Charcot-Marie-Tooth Type C Maps to Chromosome 1p34-p35

Abstract

Dominant intermediate Charcot-Marie-Tooth (DI-CMT) neuropathy is a genetic and phenotypic variant of classical CMT, characterized by intermediate nerve conduction velocities and histological evidence of both axonal and demyelinating features. We report two unrelated families with intermediate CMT linked to a novel locus on chromosome 1p34-p35 (DI-CMTC). The combined haplotype analysis in both families localized the DI-CMTC gene within a 6.3-cM linkage interval flanked by markers D1S2787 and D1S2830. The functional and positional candidate genes, Syndecan 3 (SDC3), and lysosomal-associated multispanning membrane protein 5 (LAPTM5) were excluded for pathogenic mutations.

Identification of a Location at Chromosome 19p in a Big Chinese Family with Charcot-Marie-Tooth Disease

“…Three types of dominantly inherited CMT with intermediate MNCV had been identified. CMTDI2 was linked to chromosome 10q24.1-q25.1 [10][11][12], DI-CMTC was linked to chromosome 1p34-p35 [13], and DI-CMTB was linked to chromosome 19p12-13.2 [14,15]. Mutations had been identified in DNM2 gene for DI-CMTB [5].…”

Intermediate Charcot-Marie-Tooth disease

“…YARS encodes tyrosyl-tRNA synthetase (TyrRS) and is located on chromosome 1p35.1 [44] . Aminoacyl-tRNA synthetases (ARSs) charge amino-acids onto their homologous tRNAs during protein translation.…”

“…In the North American and the Bulgarian families with YARS mutations, the clinical features were age at onset between 10 and 60 years, intermediate MNCV ranging from 25 to 58 m/s, slow progression, and moderate severity [44] .…”

Recommendations to enable drug development for inherited neuropathies: Charcot-Marie-Tooth and Giant Axonal Neuropathy

“…For example, Landsverk et al identified the gene causing a hereditary neuropathy (hereditary neuralgic amyotrophy [HNA]) that attacks the muscles responsible for controlling the movement of shoulders and arms 65 . In addition, Florian Thomas MD (St. Louis University, St. Louis, USA) and his international team have uncovered three different genetic mutations specific to dominant intermediate CMT neuropathy type C, a form of CMT disease 66 . Organizations like The American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) could be funded to support awarding of fellowships that focus on rare neuromuscular disease research.…”