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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 (+1GC) 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.

Distal hereditary motor neuronopathy is a genetically and clinically heterogeneous disorder. To date, five loci, and their relative genes, have been mapped on chromosomes 7p14, 7q11, 9q34, 11q12 and 12q24, respectively. We describe an Italian family with autosomal dominant distal HMN starting at around 30 years of age with weakness and atrophy of distal leg muscles and pyramidal features. We performed genetic linkage analysis on chromosomes 7p14, 9q34, 11q12 and 12q24. Moreover we sequenced the genes mapped to 7q11 and 12q24. Negative LOD scores excluded linkage to 7p14, 9q34, and 11q12 chromosomes in our family. No mutations were found in genes mapped to 7q11 and 12q24. In addition, because of pyramidal features, we performed the linkage analysis to all the known loci for autosomal dominant hereditary spastic paraparesis. The analysis was negative thus excluding a complicated form of autosomal dominant hereditary spastic paraparesis. These data further confirm a genetic heterogeneity within inherited motor neuronopathy.