Localization of a Gene (CMT2A) for Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 to Chromosome 1p and Evidence of Genetic Heterogeneity

Othmane, Kamel Ben; Middleton, Lefkos T.; Loprest, Lorraine; Wilkinson, Kenneth M.; Lennon, Felicia; Rozear, Marvin P.; Stajich, Jeffrey U.; Gaskell, P. C.; Roses, Allen D.; Pericak‐Vance, Margaret A.; Vance, Jeffery M.

doi:10.1006/geno.1993.1334

Cited by 143 publications

(66 citation statements)

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“…These include Charcot-Marie-Tooth type 2A (16), neuroblastoma (30), diabetes susceptibility (Idd9) (31), and resistance to plasmacytoma (Pctr2) (32).…”

Section: Discussionmentioning

confidence: 99%

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An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

Coleman

Conforti

Buckmaster

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

174

127

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Wallerian degeneration is the degeneration of the distal stump of an injured axon. It normally occurs over a time course of around 24 hr but it is delayed in the slow Wallerian degeneration mutant mouse (C57BL͞Wld s ) for up to 3 weeks. The gene, which protects from rapid Wallerian degeneration, Wld, previously has been mapped to distal chromosome 4. This paper reports the fine genetic mapping of the Wld locus, the generation of a 1.4-Mb bacterial artificial chromosome and P1 artificial chromosome contig, and the identification of an 85-kb tandem triplication mapping within the candidate region. The mutation is unique to C57BL͞Wld s among 36 strains tested and therefore is a strong candidate for the mutation that leads to delayed Wallerian degeneration. There are very few reports of tandem triplications in a vertebrate and no evidence for a mutation mechanism so this unusual mutation was characterized in more detail. Sequence analysis of the boundaries of the repeat unit revealed a minisatellite array at the distal boundary and a matching 8-bp sequence at the proximal boundary. This finding suggests that recombination between short homologous sequences (''illegitimate'' or ''nonhomologous'' recombination) was involved in the rearrangement. In addition, a duplication allele was identified in two Wld s mice, indicating some instability in the repeat copy number and suggesting that the triplication arose from a duplication by unequal crossing over.

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“…These include Charcot-Marie-Tooth type 2A (16), neuroblastoma (30), diabetes susceptibility (Idd9) (31), and resistance to plasmacytoma (Pctr2) (32).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, an axonal form of Charcot-Marie-Tooth (CMT2A) characterized by axonal loss, has been mapped to the homologous location in humans, 1p36 (16). This paper reports the identification and characterization of a tandem triplication within the Wld s candidate region.…”

mentioning

confidence: 99%

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

Coleman

Conforti

Buckmaster

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

174

127

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“…CMT1 is the demyelinating form, characterized by motor nerve conduction velocity (MNCV) below 35 m/s, whereas CMT2 is the axonal form, characterized by normal MNCV (Dyck et al, 1993). CMT2 has been linked to 3 loci on 1p35-36, 3q13-q22 and 7p14 (Ben Othmane et al, 1993;Kwon et al, 1995;Ionasescu et al, 1996). CMT1A is mostly caused by a duplication of the PMP22 gene on chromosome 17p11.2-p12 (Timmerman et al, 1992;Valentijn et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

Stojkovic

Seze

Dubourg³

et al. 2003

Clinical Neurophysiology

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Objective: To report the clinical and electrophysiological characteristics of a family presenting Charcot -Marie-Tooth disease (CMT) associated with autonomic nervous system disturbances.Methods: We studied nerve conduction values, postural adaptation, sympathetic skin reflex, the variation in heart rate by the Valsalva ratio and pupillometry in 7 members of a French family in which CMT due to a Thr124Met mutation in the myelin protein zero (MPZ) gene was diagnosed.Results: Clinical and laboratory evidence of autonomic nervous system disturbances were found in the affected individuals. The clinical phenotype was characterized by sensorimotor peripheral neuropathy, defined as axonal type by electrophysiological studies, and was associated with severe pain, bladder dysfunction, sudorimotor disturbances and abolished pupillary reflex to light. Moreover, two patients had severe restrictive respiratory insufficiency requiring noninvasive mechanical ventilation.Conclusions: Our study demonstrates that autonomic disturbances may be one of the major clinical signs associated with CMT secondary to MPZ gene mutation in codon 124. Testing of pupillary reflex allows the discrimination of affected and unaffected subjects in our family. However, involvement of the autonomic nervous system in this type of neuropathy is unclear and further studies are required to elucidate the role of the MPZ gene in the autonomic nervous system.

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“…7,8 Most recently, a novel CMT2 locus (CMT2E) has been reported on chromosome 8p21, and a disease-causing mutation was found in the neurofilament light gene. 9 Until now, significant evidence for linkage to chromosome 1p35-p36 was reported only for five CMT2A families, from Japan or North America, 2,3 making it difficult to assess the geographic distribution and clinical features of this disorder. Identification of additional pedigrees with CMT2A would allow better results.…”

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confidence: 99%

Clinical and genetic study of a large Charcot–Marie–Tooth type 2A family from southern Italy

Muglia

Zappia²,

Timmerman³

et al. 2001

Neurology

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Article abstract-The authors report a large pedigree from southern Italy with Charcot-Marie-Tooth disease type 2A (CMT2A). The clinical picture was uniform and characterized by distal muscular weakness and atrophy in the lower limbs, reduced or absent tendon reflexes mainly in the lower limbs, and mild sensory impairment in the feet. Significant linkage to the CMT2A locus on chromosome 1p35-p36 was detected. Based on informative recombination in affected individuals, the authors mapped the CMT2A gene between D1S160 and D1S170.

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Localization of a Gene (CMT2A) for Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 to Chromosome 1p and Evidence of Genetic Heterogeneity

Cited by 143 publications

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An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

Clinical and genetic study of a large Charcot–Marie–Tooth type 2A family from southern Italy

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Localization of a Gene (CMT2A) for Autosomal Dominant Charcot-Marie-Tooth Disease Type 2 to Chromosome 1p and Evidence of Genetic Heterogeneity

Cited by 143 publications

References 0 publications

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld s ) mouse

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld s ) mouse

Autonomic and respiratory dysfunction in Charcot–Marie–Tooth disease due to Thr124Met mutation in the myelin protein zero gene

Clinical and genetic study of a large Charcot–Marie–Tooth type 2A family from southern Italy

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An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse

An 85-kb tandem triplication in the slow Wallerian degeneration ( Wld ^s ) mouse