SPECTRUM OF MUTATIONS IN FINNISH PATIENTS WITH CHARCOT-MARIE-TOOTH-DISEASE AND RELATED NEUROPATHIES

Our patient material included families and sporadic patients of Finnis h origin with the diagnosis of Charcot Marie-Tooth (CMT) disease types 1 and 2, Deferine-Sottas syndrome (DSS), and hereditary neuropathy wi th liability to pressure palsies (HNPP). We screened for mutations in the peripheral myelin protein genes connexin 32 (Cx32), myelin protein zero (P-0) and peripheral myelin protein 22 (PMP22) by direct sequenc ing. All patients chosen for mutation screening were negative for the 1.5 Mb duplication/deletion at 17p11.2-p12. Eleven Cx32 mutations were found in 12 families, six with a CMT2 diagnosis, three with a CMT1 di agnosis and three with unclassified CMT. The total number of patients in these 12 CMTX families was 61, giving a minimum prevalence of 1.2/1 00,000 for CMTX in Finland. Four of the mutations, Pro58Arg, Pro172Leu , Asn175Asp and Leu204Phe, have not been previously reported. One male patient with an early onset CMT had a double Cx32 mutation, Arg22Gln and Val63Ile. The double de novo mutation was found to be of maternal grandpaternal origin. In the P-0 gene a Ser78Leu mutation was found in one family with severe CMT1 and a de novo Tyr82Cys mutation was found in one DSS patient. Both mutations have been previously reported in o ther CMT1 families. A novel PMP22 mutation, deletion of Phe84, was fou nd in one sporadic DSS patient. Our mutation screening results show th e necessity of molecular diagnosis, in addition to clinical and electr ophysiological evaluation, for proper subtyping of the disease and for accurate genetic counseling. (C) 1998 Wiley-Liss, Inc.