A DE-NOVO CASE OF HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES (HNPP) OF MATERNAL ORIGIN - A NEW MECHANISM FOR DELETION IN 17P11.2

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant neuropathy, most often associated with a deletion o f the 17p11.2 region, which is duplicated in 70% of patients with Char cot-Marie-Tooth type 1 (CMT1A). Most de novo CMT1A and HNPP cases have been of paternal origin. A rare case of de novo HNPP of maternal orig in was analysed to determine the underlying mechanism. Affected indivi duals in the family carried a deletion corresponding to the CMT1A/HNPP monomer unit associated with a rearrangement of the CMT1A-REP sequenc es. Segregation analysis of 17p11-p12 markers in the family indicated that the deletion was not generated by unequal crossing over between h omologous 17 chromosomes, as in de novo cases from paternal origin, bu t rather by an intrachromosomal rearrangement. Two distinct mechanisms can therefore lead to the same 17p11.2 deletion. This result suggests that intrachromosomal rearrangement may be specific to maternal trans missions.