CMT 4B2 research from INS, NRC,PLM, Cosenza

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Research from J Peripher Nerv Syst. 2004 Jun;9(2):124.

A splice-junction mutation in SBF2 gene causes autosomal recessive

charcot-marie-tooth disease (CMT4B2) in a family from southern italy.

Conforti F, Muglia M, Mazzei R, Valentino P, Patitucci A, Bono F,

Magariello A, Sprovieri T, Senderek J, Bergmann C, Nistico R, e

A, Peluso G, Quattrone A.

Institute of Neurological Sciences, National Research Council, Piano

Lago di Mangone, Cosenza.

Autosomal recessive Charcot-Marie-Tooth disease type 4 (CMT4) comprises

a group of clinically and genetically heterogeneous disorders of the

peripheral nervous system. At least 10 loci are responsible for

autosomal recessive CMT and six genes have been identified so far. In

this study, we report a small pedigree with a recessive form of CMT

(CMT4B) from Southern Italy. There were six individuals in two

generations with two affected subjects. We performed haplotype analysis

using highly polymorphic microsatellite markers located on chromosome

11p15. Subsequently, the coding region of the Sbf2 gene was sequenced by

using primers flanking intron-exon boundaries. Mutational screening of

Sbf2 revealed a homozygous mutation in the splice-junction

donor-acceptor site of intron 32 (+1G-->C) in the affected patients. The

variation was also confirmed by digestion with restriction enzyme Alu I

and it was absent in 100 control chromosomes examined. This is the first

finding of a mutation in the Sbf2 gene that alters the correct splicing

of the gene. Furthermore, these data confirm that mutations in the Sbf2

gene are causative of CMT4B2.