Program Nr: 620 for the 2006 ASHG Annual Meeting

Detection of Duplication/Deletion of the PMP22 Gene in Patients with Charcot-Marie-Tooth Disease Type 1A and Hereditary Neuropathy with Liability to Pressure Palsy. M. Rostami, M. Dehghanmanshadi, S.M. Seyedhasani, A. Ebrahimi, M. Tonekaboni, M. Houshmand. medical genetic, NIGEB, Tehran, Tehran, Iran.
   Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of hereditary peripheral neuropathies. The clinical characteristics of the disease include distal symmetric muscle weakness, atrophy, bilateral pes cavus, and diminished or absent deep tendon reflexes. Peripheral nerve conduction velocities are often severely reduced. In hereditary neuropathy with liability to pressure palsy (HNPP), recurrent peripheral nerve palsies (e.g., ulnar nerve, median nerve, and peroneal nerve palsies) occur because of minor compression trauma, whereas foot deformity is less frequently observed than it is in CMT. Nerve conduction velocities are significantly reduced at compression sites of peripheral nerves. Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common form of CMT (1, 2). A 1.5-Mb duplication on chromosome 17p11.2-p12 (CMT1A duplication) caused by a misalignment of the CMT1A repeat sequences (CMT1A-REPs) is associated with Charcot-Marie-Tooth disease type 1A (CMT1A). A hotspot of crossover breakpoints located in a 3.2-kb region of the CMT1A-REPs accounts for three-quarters of the rearrangements in CMT1A patients. In contrast, deletion of the PMP22 characteristically results in HNPP. Point mutation in the PMP22 may result in CMT1A or HNPP. Thus heterozygous carriers of the deletion (HNPP) or duplication (CMT1A) have one or three copies of the PMP22, respectively.We used some methods for study of this gene: PCR-based diagnostic method to detect a recombination Hotspot associated with the CMT1A duplication Methods for molecular diagnosis of CMT1A use Southern blot and/or amplification by PCR of polymorphic poly (AC) repeats(microsatellites) located within the duplicated region, or the detection of junction fragments specific for the duplication. Real-time quantitative PCR using SYBR Green I to detect the PMP22 duplication and deletion.