Applicazioni della Real Time PCR nello screening della malattia di Charcot-Marie-Tooth tipo I A

- 5 - Abstract ABSTRACT Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous group of disorders sharing the same clinical phenotype, characterized by distal limb muscle wasting and weakness, usually with skeletal deformities, distal sensory loss and abnormalities of deep tendon reflexes; the degree of severity can vary greatly from patient to patient, even within the same family. This work focuses on the most common form of 'demyelinating' neuropathy, Charcot- Marie-Tooth 1A disease and on a technique used to detect subjects affected by this disease: the Real Time PCR. Charcot-Marie-Tooth 1A disease is caused by a 1.4 Mb duplication in the 17p11.2 chromosomal region encompassing the Peripheral Myelin Protein gene (PMP22). This region is flanked by tandem repeated sequences called CMT1A-REPs, often responsible of the unequal crossing over during meiosis; the result of the unequal crossing-over is the presence of three copies of PMP22. The PMP22 gene encodes for the Peripheral Myelin Protein 22 (PMP22); the protein play an important role in the regulation of the correct function of Schwann cells, because it seems to be a structural protein. The consequence of the over-expression of the gene has profound effects on the development and maintenance of myelin of the peripheral nerves. The routine molecular tests actually used to detect the duplication in CMT1A are: - analysis of a recombinant hot spot of 3.2 Kb by PCR; this method is useful to detect the 63% of cases of duplication;