Alternatively sized duplication in Charcot — Marie — Tooth disease type 1A

Valentijn, Linda J.; Baas, Frank; Zorn, I.; Hensels, G. W.; Visser, Marjolein; Bolhuis, P. A.

doi:10.1093/hmg/2.12.2143

Cited by 52 publications

(22 citation statements)

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“…Four families with alternate size duplication or deletion were reported previously (Ionasescu et al 1993;Palau et al 1993;Valentijn et al 1993;Chapon et al 1996). Genetic studies with a few markers showed that the proximal break points of these cases are located close to or within the proximal CMT1A-REP, and the distal break points mapped between PMP22 and D17S125 (Ionasescu et al 1993;Palau et al 1993;Valentijn et al 1993;Chapon et al 1996).…”

Section: Relevance To Cmt1a/hnpp Genomic Disordersmentioning

confidence: 96%

“…A formal possibility exists that minor dosage effect of genes other than PMP22 in this 1.4-Mb region somehow contribute to the variability of phenotypic manifestations or a combination of phenotypes (e.g., CMT + connective tissue disorder). Furthermore, there are rare case reports of smaller duplications (Ionasescu et al 1993;Palau et al 1993;Valentijn et al 1993) or deletion (Chapon et al 1996), raising the question as to whether such rare recombination events are mediated by other repeat units in this region.…”

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confidence: 99%

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The 1.4-Mb CMT1A Duplication/HNPP Deletion Genomic Region Reveals Unique Genome Architectural Features and Provides Insights into the Recent Evolution of New Genes

Inoue¹,

Dewar²,

Katsanis³

et al. 2001

Genome Res.

134

117

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Duplication and deletion of the 1.4-Mb region in 17p12 that is delimited by two 24-kb low copy number repeats (CMT1A–REPs) represent frequent genomic rearrangements resulting in two common inherited peripheral neuropathies, Charcot-Marie-Tooth disease type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP). CMT1A and HNPP exemplify a paradigm for genomic disorders wherein unique genome architectural features result in susceptibility to DNA rearrangements that cause disease. A gene within the 1.4-Mb region,PMP22, is responsible for these disorders through a gene-dosage effect in the heterozygous duplication or deletion. However, the genomic structure of the 1.4-Mb region, including other genes contained within the rearranged genomic segment, remains essentially uncharacterized. To delineate genomic structural features, investigate higher-order genomic architecture, and identify genes in this region, we constructed PAC and BAC contigs and determined the complete nucleotide sequence. This CMT1A/HNPP genomic segment contains 1,421,129 bp of DNA. A low copy number repeat (LCR) was identified, with one copy inside and two copies outside of the 1.4-Mb region. Comparison between physical and genetic maps revealed a striking difference in recombination rates between the sexes with a lower recombination frequency in males (0.67 cM/Mb) versus females (5.5 cM/Mb). Hypothetically, this low recombination frequency in males may enable a chromosomal misalignment at proximal and distal CMT1A–REPs and promote unequal crossing over, which occurs 10 times more frequently in male meiosis. In addition to three previously described genes, five new genes (TEKT3, HS3ST3B1, NPD008/CGI-148, CDRT1, andCDRT15) and 13 predicted genes were identified. Most of these predicted genes are expressed only in embryonic stages. Analyses of the genomic region adjacent to proximal CMT1A–REP indicated an evolutionary mechanism for the formation of proximal CMT1A–REP and the creation of novel genes by DNA rearrangement during primate speciation.

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Section: Relevance To Cmt1a/hnpp Genomic Disordersmentioning

confidence: 96%

mentioning

confidence: 99%

The 1.4-Mb CMT1A Duplication/HNPP Deletion Genomic Region Reveals Unique Genome Architectural Features and Provides Insights into the Recent Evolution of New Genes

Inoue¹,

Dewar²,

Katsanis³

et al. 2001

Genome Res.

134

117

View full text Add to dashboard Cite

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“…The duplication causes CMT1A and the deletion causes HNPP (see paragraph HNPP). Rarely, smaller duplications have been found but all of them contain the PMP22 gene [199]. Patients homozygous for the duplication are usually more severely affected than heterozygote ones [114,119].…”

Section: Cmt1mentioning

confidence: 99%

Clinical features and molecular genetics of hereditary peripheral neuropathies

Kuhlenbäumer

Young

Hünermund

et al. 2002

Journal of Neurology

129

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Hereditary peripheral neuropathies are the most common monogenetically inherited diseases of the nervous system. The prevalence of the Hereditary Motor and Sensory Neuropathy Type 1A (HMSN 1A or Charcot-Marie-Tooth Neuropathy 1A, CMT1A) alone is estimated to be as high as 1/5000. In 1991, a duplication on chromosome 17p11.2 was identified as the causative genetic defect of CMT1A. Since then causative mutations in 17 genes have been identified. This review summarises the clinical and molecular genetic features of primary inherited neuropathies. It is aimed primarily at clinicians and geneticists. Therefore less emphasis is placed on the pathology and the (often unknown) underlying biological disease mechanisms.

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“…Previously, we have shown that FISH can be used to rapidly and reliably detect microduplications and microdeletions involving the PMP22 locus, causing CMT1A and HNPP, respectively ). An additional advantage of the FISH-based assay, as compared with other diagnostic approaches, such as PFGE, is that FISH will detect altered-size duplications or deletions of the region containing the PMP22 gene (Valentijn et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Prenatal diagnosis of Charcot-Marie-Tooth disease type 1A by interphase fluorescencein situ hybridization

1999

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To develop an index to measure alveolar macrophage activity, the fluorescent technique for detection of calcium flux was paid special attention. In this study, a parallel luminescence measuring system was remodelled for fluorescence measurement using a 96‐well microplate. The fluorescence indicators widely used to measure cytosolic free calcium ion concentration require excitation at ultraviolet (UV) wavelengths. Instruments to produce UV wavelengths are expensive compared to those used to produce visible wavelengths, and UV wavelengths are potentially injurious to cells. To avoid these problems, Fluo 3 (excitation wavelength in the visible range) was used as the fluorescent dye for detecting calcium ions. The parallel luminometer was remodelled successfully for fluorescent measurement as assessed by the results obtained from the measurements of a common fluorescent dye, fluorescein. Concentrations of free calcium ions were measured using Fluo 3 at 37°C to consider the measurement of calcium flux in living cells. Although a linear relationship between concentrations of free calcium ions and fluorescence were observed, a diminution of fluorescence over time was also observed. To measure calcium flux in living cells, further instrumental and experimental improvements are thus needed. Copyright © 1999 John Wiley & Sons, Ltd.

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Alternatively sized duplication in Charcot — Marie — Tooth disease type 1A

Cited by 52 publications

References 0 publications

The 1.4-Mb CMT1A Duplication/HNPP Deletion Genomic Region Reveals Unique Genome Architectural Features and Provides Insights into the Recent Evolution of New Genes

The 1.4-Mb CMT1A Duplication/HNPP Deletion Genomic Region Reveals Unique Genome Architectural Features and Provides Insights into the Recent Evolution of New Genes

Clinical features and molecular genetics of hereditary peripheral neuropathies

Prenatal diagnosis of Charcot-Marie-Tooth disease type 1A by interphase fluorescencein situ hybridization

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