CMT 1A: The 5' regulatory sequence of the PMP22 in the patients with

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Acta Biochim Pol. 2010 Sep 15

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

disease.

Sinkiewicz-Darol E, Kabzi & #324;ska D, Moszy & #324;ska I, Kocha & #324;ski A.

Neuromuscular Unit, Mossakowski Medical Research Centre, Polish Academy of

Sciences, Warsaw, Poland.

Abstract

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 of 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.

PMID: 20842290 [PubMed - as su