Charcot-Marie-Tooth type 4B2 demyelinating neuropathy in miniature Schnauzer dogs caused by a novel splicing SBF2 (MTMR13) genetic variant: a new spontaneous clinical model

This study reports the first genetic variant in Miniature Schnauzer dogs responsible for the occurrence of a demyelinating peripheral neuropathy with abnormally folded myelin. This discovery establishes a genotype/phenotype correlation in affected Miniature Schnauzers that can be used for the diagnosis of these dogs. It further supports the dog as a natural model of a human disease; in this instance, Charcot-Marie-Tooth disease. It opens avenues to search the biological mechanisms responsible for the disease and to test new therapies in a non-rodent large animal model. In particular, recent gene editing methods that led to the restoration of dystrophin expression in a canine model of muscular dystrophy could be applied to other canine models such as this before translation to humans

Chronic inflammatory demyelinating polyneuropathy as a complication of cat scratch disease

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Hereditary neuropathy with liability to pressure palsies with a small deletion interrupting the PMP22 gene

Institute of Neurology, University Medical Centre Nijmegen, Nijmegen, The Netherlands Hereditary neuropathy with liability to pressure palsies is associated with a deficiency in the Peripheral Myelin Protein 22 (PMP22). Most hereditary neuropathy with liability to pressure palsies cases are caused by a deletion of a 1.5 Mb region on chromosome 17p11.2-12 encompassing the PMP22 gene. We describe a hereditary neuropathy with liability to pressure palsies family that lacks the common deletion, but carries a small deletion spanning the 3' region of the PMP22 gene, causing only a partial deletion of one copy of the gene

Study on the gene and phenotypic characterisation of autosomal recessive demyelinating motor and sensory neuropathy (Charcot-Marie-Tooth disease) with a gene locus on chromosome 5q23-q33

OBJECTIVES—To report the occurrence of the autosomal recessive form of demyelinating Charcot-Marie-Tooth disease (CMT) with a locus on chromosome 5q23-33 in six non-related European families, to refine gene mapping, and to define the disease phenotype.
METHODS—In an Algerian patient with autosomal recessive demyelinating CMT mapped to chromosome 5q23-q33 the same unique nerve pathology was established as previously described in families with a special form of autosomal recessive demyelinating CMT. Subsequently, the DNA of patients with this phenotype was tested from five Dutch families and one Turkish family for the 5q23-q33 locus.
RESULTS—These patients and the Algerian families showed a similar and highly typical combination of clinical and morphological features, suggesting a common genetic defect. A complete cosegregation for markers D5S413, D5S434, D5S636, and D5S410 was found in the families. Haplotype construction located the gene to a 7 cM region between D5S643 and D5S670. In the present Dutch families linkage disequilibrium could be shown for various risk alleles and haplotypes indicating that most of these families may have inherited the underlying genetic defect form a common distant ancestor.
CONCLUSIONS—This study refines the gene localisation of autosomal recessive demyelinating CMT, mapping to chromosome 5q23-33 and defines the phenotype characterised by a precocious and rapidly progressive scoliosis in combination with a relatively mild neuropathy and a unique pathology. Morphological alterations in Schwann cells of the myelinated and unmyelinated type suggest the involvement of a protein present in both Schwann cell types or an extracellular matrix protein rather than a myelin protein. The combination of pathological features possibly discerns autosomal recessive demyelinating CMT with a gene locus on chromosome 5q23-33 from other demyelinating forms of CMT disease.