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A splice‐junction mutation in SBF2 gene causes autosomal recessive charcot‐marie‐tooth disease (CMT4B2) in a family from southern italy
Author(s) -
Conforti FL,
Muglia M,
Mazzei R,
Valentino P,
Patitucci A,
Bono F,
Magariello A,
Sprovieri T,
Senderek J,
Bergmann C,
Nisticò R,
Gabriele AL,
Peluso G,
Quattrone A
Publication year - 2004
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1085-9489.2004.009209bn.x
Subject(s) - genetics , biology , exon , gene , haplotype , intron , mutation , genetic linkage , microbiology and biotechnology , allele
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.