Clinical and Genetic Studies on Giant Axonal Neuropathy

Objective To investigate 2 giant axonal neuropathy (GAN) families and detect the mutation of GAN gene in their family.Methods The encoding exons of GAN gene were amplified from genomic DNA of the probands and their parents by PCR and directly sequenced after getting purified.Results No.1 proband manifested typical neurological symptoms and pathological abnormalities.The case of the girl had 2 heterozygous missense mutations in GAN gene:1.c.224TA in exon 2,which results in the amino acid change of L75H;her mother was a heterozygote of this mutation and had normal phenotype,while her father had normal genotype in this site;2.c.1634GA in exon 10,her father was a heterozygote of this mutation and had normal phenotype,while her mother had normal genotype in this site.Both of the mutations cause amino acid changes in the gigaxonin protein.No mutation was detected in proband No.2.Conclusions In family 1,missense mutation of c.224TA and missense mutation of c.1634GA in GAN gene cause the phenotype of GAN in the proband.The girl′s parents are heterozygotes of the disease without symptoms.There may be other mode of inheritance in family 2.