Charcot–Marie–Tooth disease: Inherited neuropathies revisited

Matiasek, Kaspar; Drögemüller, Cord

doi:10.1016/j.tvjl.2011.03.002

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Dogs are medically surveyed on a regular basis and the dog population consists of several partially inbred breeds with known, and from time to time new, genetic disorders segregating in most of the breeds. When considering the extensive amount of dog genome resources and rapidly increasing technologies, canine disorders have a great potential for serving as models for analogous human diseases [13].…”

Section: Discussionmentioning

confidence: 99%

A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy

et al. 2013

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The first cases of early-onset progressive polyneuropathy appeared in the Alaskan Malamute population in Norway in the late 1970s. Affected dogs were of both sexes and were ambulatory paraparetic, progressing to non-ambulatory tetraparesis. On neurologic examination, affected dogs displayed predominantly laryngeal paresis, decreased postural reactions, decreased spinal reflexes and muscle atrophy. The disease was considered eradicated through breeding programmes but recently new cases have occurred in the Nordic countries and the USA. The N-myc downstream-regulated gene (NDRG1) is implicated in neuropathies with comparable symptoms or clinical signs both in humans and in Greyhound dogs. This gene was therefore considered a candidate gene for the polyneuropathy in Alaskan Malamutes. The coding sequence of the NDRG1 gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a Gly98Val amino acid substitution. This substitution was categorized to be “probably damaging” to the protein function by PolyPhen2 (score: 1.000). Subsequently, 102 Alaskan Malamutes from the Nordic countries and the USA known to be either affected (n = 22), obligate carriers (n = 7) or healthy (n = 73) were genotyped for the SNP using TaqMan. All affected dogs had the T/T genotype, the obligate carriers had the G/T genotype and the healthy dogs had the G/G genotype except for 13 who had the G/T genotype. A protein alignment showed that residue 98 is conserved in mammals and also that the entire NDRG1 protein is highly conserved (94.7%) in mammals. We conclude that the G>T substitution is most likely the mutation that causes polyneuropathy in Alaskan Malamutes. Our characterization of a novel candidate causative mutation for polyneuropathy offers a new canine model that can provide further insight into pathobiology and therapy of human polyneuropathy. Furthermore, selection against this mutation can now be used to eliminate the disease in Alaskan Malamutes.

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Section: Discussionmentioning

confidence: 99%

A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy

et al. 2013

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“…Naturally occurring neuropathies in dogs are increasingly recognized as models for human neuropathies [24,25]. As opposed to experimental rodents, dogs naturally develop similar diseases to humans.…”

Section: Cmt4dmentioning

confidence: 99%

Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D

Skedsmo

Espenes

Tranulis

et al. 2021

Neuromuscular Disorders

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Charcot–Marie–Tooth disease: Inherited neuropathies revisited

Cited by 2 publications

References 13 publications

A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy

A Gly98Val Mutation in the N-Myc Downstream Regulated Gene 1 (NDRG1) in Alaskan Malamutes with Polyneuropathy

Impaired NDRG1 functions in Schwann cells cause demyelinating neuropathy in a dog model of Charcot-Marie-Tooth type 4D

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