[Two novel pathogenic mutations of GAN gene identified in a patient with giant axonal neuropathy].
OBJECTIVE
To explore the disease-causing mutations in a patient suspected for giant axonal neuropathy(GAN).


METHODS
Target sequence capture sequencing was used to screen potential mutations in genomic DNA extracted from peripheral blood sample of the patient. Sanger sequencing was applied to confirm the detected mutation. The mutation was verified among 400 GAN alleles from 200 healthy individuals by Sanger sequencing. The function of the mutations was predicted by bioinformatics analysis.


RESULTS
The patient was identified as a compound heterozygote carrying two novel pathogenic GAN mutations, i.e., c.778G>T (p.Glu260Ter) and c.277G>A (p.Gly93Arg). Sanger sequencing confirmed that the c.778G>T (p.Glu260Ter) mutation was inherited from his father, while c.277G>A (p.Gly93Arg) was inherited from his mother. The same mutations was not found in the 200 healthy individuals. Bioinformatics analysis predicted that the two mutations probably caused functional abnormality of gigaxonin.


CONCLUSIONS
Two novel GAN mutations were detected in a patient with GAN. Both mutations are pathogenic and can cause abnormalities of gigaxonin structure and function, leading to pathogenesis of GAN. The results may also offer valuable information for similar diseases.
Shanghai Institute of Medical Genetics, Shanghai Children's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200040, China; Key Laboratory of Embryo Molecular Biology, Ministry of Health, Shanghai Key Laboratory of Embryo and Reproduction Engineering, Shanghai 200040, China. zhrren1225@163.com.
Juan
J
Wang
Qingwen
Q
Ma
Qin
Q
Cai
Yanna
Y
Liu
Wei
W
Wang
Zhaorui
Z
Ren
D000595:Amino Acid Sequence; D002648:Child; D019295:Computational Biology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D056768:Giant Axonal Neuropathy / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D017422:Sequence Analysis, DNA
D003598:Cytoskeletal Proteins; C416508:GAN protein, human