Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a)

Raeymaekers, Peter; Timmerman, Vincent; Nelis, Eva; Jonghe, Peter De; Hoogendijk, Jessica E.; Baas, Frank; Barker, David F.; Martin, J. J.; Visser, Marjolein; Bolhuis, P. A.

doi:10.1016/0960-8966(91)90055-w

Cited by 586 publications

(301 citation statements)

References 9 publications

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“…Thus, PMP-22 gene could be assigned to band 17p11.2. The CMT 1A has been localized to 17pll.2-p12 by genetic linkage and cytogenetic analyses (McAlpine et al, 1990;Patel et al, 1990;Vance et al, 1991;Lupski et al, 1991;Raeymaekers et al, 1991). The present result was within the map position of the CMT IA gene by genetic linkage analysis, and strongly indicated that PMP-22 gene is a candidate gene for the CMT IA.…”

Section: Results And~discussionsupporting

confidence: 70%

Localization of PMP-22 gene (candidate gene for the Charcot-Marie-Tooth disease 1a) to band 17p11.2 by direct r-banding fluoreschenceIn situ hybridization

et al. 1992

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Section: Results And~discussionsupporting

confidence: 70%

Localization of PMP-22 gene (candidate gene for the Charcot-Marie-Tooth disease 1a) to band 17p11.2 by direct r-banding fluoreschenceIn situ hybridization

et al. 1992

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“…CMT1A and hereditary neuropathy with liability to pressure palsies (HNPP) are two inherited autosomal dominant peripheral neuropathies that are both associated with genomic rearrangements on human chromosome 17 (Lupski et al, 1991;Raeymaekers et al, 1991). Duplication of a 1.5 megabase region spanning chromosome 17p11.2-p12 leads to CMT1A, whereas the reciprocal deletion causes HNPP Chance et al, 1993;Reiter et al, 1996).…”

Section: Abstract: Pmp22; Peripheral Myelin Protein-22; Peripheral Nmentioning

confidence: 99%

Heterozygous Peripheral Myelin Protein 22-Deficient Mice Are Affected by a Progressive Demyelinating Tomaculous Neuropathy

et al. 1997

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Hereditary neuropathy with liability to pressure palsy (HNPP) is associated with a heterozygous 1.5 megabase deletion on chromosome 17 that includes the peripheral myelin protein (PMP) gene PMP22. We show that heterozygous PMP22 knock-out mice, which carry only one functional pmp22 allele and thus genetically mimic HNPP closely, display similar morphological and electrophysiological features as observed in HNPP nerves. As reported previously, focal hypermyelinating structures called tomacula, the pathological hallmarks of HNPP, develop progressively in young PMP22 ϩ/0 mice. By following the fate of tomacula during aging, we demonstrate now that these mutant animals are also interesting models for examining HNPP disease mechanisms. Subtle electrophysiological abnormalities are detected in PMP22 ϩ/0 mice Ͼ1 year old, and a significant number of abnormally swollen and degenerating tomacula are present. Thinly myelinated axons and supernumerary Schwann cells forming onion bulbs as fingerprints of repeated cycles of demyelination and remyelination are also encountered frequently. Quantitative analyses using electron microscopy on cross sections and light microscopy on single teased nerve fibers suggest that tomacula are intrinsically unstable structures that are prone to degeneration; however, the severity of morphological and electrophysiological abnormalities in PMP22 ϩ/0 mice is variable. These combined findings are reminiscent of the disease progression in HNPP and offer a possible explanation about why some HNPP patients develop a chronic motor and sensory neuropathy later in life that resembles demyelinating forms of Charcot-MarieTooth disease by both morphological and clinical criteria.

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“…Autosomaldominant CMT1 is the most frequent form (approximately 70% of CMT patients; Nelis et al 1996), and the genetic defect in the majority of cases is linked to chromosome 17p11.2-p12 (reviewed by Suter & Patel, 1994). This specific CMT1 subtype has been designated CMT1A and human molecular genetics has demonstrated a tight association with an intrachromosomal duplication of 1.5 Mb (Lupski et al 1991a;Raeymaekers et al 1991). Increased gene dosage was proposed as the underlying disease mechanism mainly based on the observation of abnormal nerve conduction velocity (NCV) in patients with segmental trisomies in this region ).…”

Section: Genetics Of Hmsnmentioning

confidence: 99%

Mouse genetics in cell biology

Mansuy¹,

Suter²

2000

Exp. Physiol.

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One of the most fascinating challenges in modern cell biology is the unravelling of the molecular mechanisms underlying the development and formation of functional organs, and the maintenance and regeneration of vertebrate tissues. In such processes, cell-cell interactions, mediated by direct contacts or secreted factors, and cell-extracellular matrix interactions are essential for the control of cell proliferation, migration, differentiation and death. These events are mediated by numerous molecular signals that have to be integrated within the cell to activate specific sets of regulatory factors responsible for correct spatial and temporal gene regulation. We are still far away from a complete understanding of these complex events at a molecular level but molecular genetic and genomic approaches have provided valuable tools and methodologies for the study of complex cellular functions in vivo. In particular, the development of reverse genetic methods such as transgene expression and gene targeting has allowed substantial progress in the understanding of the molecular mechanisms of cell-cell and cell-extracellular interactions. Although initially limited by a lack of spatial and temporal specificity, these approaches have recently undergone major developments partly overcoming these limitations, and have brought novel perspective into the application of genetic tools for the study of highly complex biological functions. To illustrate the power of genetic approaches in cell biology, we will describe in the first part of this review, several examples of mutant mice models that have allowed studies of developmental processes and neuron-glia interactions in the peripheral nervous system (PNS). The second part of the review will focus on recent advances of genetic approaches by describing the major methodologies, their latest developments and a few remarkable examples of their application in neurobiology and cancer research. Cell-cell and cell-extracellular matrix interactionsNeuronal and glial cell interactions in the nervous system Peripheral nerves are well suited to the study of the mechanisms of cell-cell interactions in organogenesis, a process in which cells determine the fate of their neighbours (Taylor & Suter, 1997;Jessen & Mirsky, 1999). This is exemplified in the process of myelination where two cell types, neurons and Schwann cells, exhibit a profound influence on each other. While axons regulate the proliferation and differentiation of Schwann cells, the latter are the main determinants of axon calibre and ion channel distribution. It has recently become clear that this cellular interdependence is not restricted to postnatal events, but that embryonic Schwann cell precursors and neurons also support each other for survival during critical periods of development. Furthermore, disturbance of the delicate balance between neuron and glia interactions by genetic manipulation has been revealed to be Genetic methodologies have provided powerful means for investigating the cellular and molecular mechanisms of ...

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Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT 1a)

Cited by 586 publications

References 9 publications

Localization of PMP-22 gene (candidate gene for the Charcot-Marie-Tooth disease 1a) to band 17p11.2 by direct r-banding fluoreschenceIn situ hybridization

Localization of PMP-22 gene (candidate gene for the Charcot-Marie-Tooth disease 1a) to band 17p11.2 by direct r-banding fluoreschenceIn situ hybridization

Heterozygous Peripheral Myelin Protein 22-Deficient Mice Are Affected by a Progressive Demyelinating Tomaculous Neuropathy

Mouse genetics in cell biology

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