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2010 | 57 | 3 | 373-377
Article title

The 5' regulatory sequence of the PMP22 in the patients with Charcot-Marie-Tooth disease

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EN
Abstracts
EN
Little is known about the molecular background of clinical variability of Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP). The CMT1A and HNPP disorders result from duplication and deletion of the PMP22 gene respectively. In a series of studies performed on affected animal transgenic models of CMT1A disease, expression of the PMP22 gene (gene dosage) was shown to correlete with severity of CMT course (gene dosage effect). In this study we hypothesized that single nucleotide polymorphisms (SNPs) located within the 5' regulatory sequence of PMP22 gene may be responsible for the CMT1A/HNPP clinical variability. We have sequenced the PMP22 5' upstream regulatory sequence in a group of 45 CMT1A/HNPP patients harboring the PMP22 duplication (37) /deletion (8). We have identified five SNPs in the regulatory sequence of the PMP22 gene. Three of them i.e. -819C>T, -4785G>T, -4800C>T were detected both in the patients and in the control group. Thus, their pathogenic role in the regulation of the expression of the PMP22 gene seems not to be significant. Two SNPs i.e. -4210T>C and -4759T>A were found only in the CMT patients. Their role in the regulation of the PMP22 gene expression can not be excluded. Additionally we have detected the Thr118Met variant in exon 4 of the PMP22 gene, which was previously reported by other authors, in one patient. We conclude that the 5' regulatory sequence of the PMP22 gene is conserved at the nucleotiode level, however rarely occurring SNPs variant in the PMP22 regulatory sequence may be associated with the gene dosage effect.
Publisher

Year
Volume
57
Issue
3
Pages
373-377
Physical description
Dates
published
2010
received
2010-05-27
revised
2010-09-03
accepted
2010-09-05
(unknown)
2010-09-15
Contributors
  • Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
  • Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
  • Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
  • Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warszawa, Poland
References
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Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv57p373kz
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