mutations research in CMT from Milan

[Guest guest]

Research from J Peripher Nerv Syst. 2004 Jun;9(2):117.

Molecular analysis of the litaf/simple and prx genes in patients with

demyelinating charcot-marie-tooth (CMT) disease.

Milani M, Cesari M, Baratta S, Caccia C, Balestrini M, Riva D, Pareyson

D, Taroni F.

Istituto Nazionale Neurologico " C. Besta " , Milan, Italy.

At least 20 genetic loci and 12 genes have been associated with the

demyelinating form of CMT disease and related disorders. Mutations in

the LITAF/SIMPLE gene (CMT1C; 16p13.3) have been recently suggested to

be a relatively common cause of CMT1 after the CMT1A duplication and

GJB1/Cx32 mutations (Saifi et al., ASHG 2003). We have screened for

LITAF mutations a group of 120 CMT1 patients negative for CMT1A-dup,

MPZ, PMP22 and GJB1/Cx32. We have so far identified two relatively

frequent polymorphisms and 3 severely affected patients who exhibited

unique abnormal DHPLC profiles in ex2 and ex3. Unlike the dominant

forms, only a limited number of loci have been linked to the rare

recessive forms (AR-CMT). The 4.9-kb coding region of the periaxin gene

(PRX, CMT4F) was scanned for mutations by DHPLC and sequence analysis in

a group of 30 CMT1A/MPZ/PMP22/Cx32-negative patients with severe

demyelinating neuropathy. Three novel frameshift and nonsense mutations

were identified in two AR families. Interestingly, in one family, two

siblings exhibited different disease severity and were found to be

compound heterozygotes for two mutations affecting the long (L-periaxin)

but not the short (S-periaxin) variant of the protein, suggesting that

S-periaxin expression may account for clinical variability in these

patients.