Molecular genetic analysis of Charcot-Marie-Tooth 1A duplication in Norwegian patients by quantitative photostimulated luminescence imaging

Around 70% of Charcot-Marie-Tooth 1 (CMT1) cases are caused by a dominantly inherited 1.5-Mb duplication at 17p11.2-12 (CMT1A). Using photostimulated luminescence (PSL) imaging of MspI Southern blots, hybridization signals of the probe pVAW409R3a in relation to cohybridized probe SF85a, were densito metrically quantified and an RFLP allele-band ratio determined. A total of 55 Norwegian CMT patients and 16 asymptomatic family members from 26 separa te families, clinically and neurophysiologically classified as CMT1 (n = 46 ) and CMT2 (n = 9). were studied. Thirty-two of 46 CMT1 cases (69.6%), all heterozygous but one homozygous for the pVAW409R3a MspI polymorphism, from 12 of 21 families (57.1%) were positive for the CMT1A duplication. In autos omal dominant familial cases (n = 30) 26 of 30 cases (86.7%), all heterozyg ous, from six of seven families (85.7%) were positive for duplication. None of the CMT2 patients, asymptomatic family members or healthy controls were positive for duplication. The CMT1A frequency of duplication in Norwegian CMT1 patients is in general agreement with those reported in other European countries and the present results show that quantitative densitometric PSL imaging is a highly reliable test in diagnosing CMT1A duplication, (C) 200 1 Elsevier Science B.V. All rights reserved.