Two novel mutations in theGAN gene causing giant axonal neuropathy
Two novel mutations in theGAN gene causing giant axonal neuropathy作者机构:Medical Specialties HospitalBoulevard Milenio 130San Carlos la Roncha37660 LeonGuanajuatoMexico Department of Gene ticsNational Institute of R ehabilitationAvenue Mexico-Xochimilco 28914389 Me xico CityMexico Department ofHis tologySchool ofMedicineAutonomous University oft heS tate ofN uevo LeonMonterreyMexico
出 版 物:《World Journal of Pediatrics》 (世界儿科杂志(英文版))
年 卷 期:2018年第14卷第3期
页 面:298-304页
核心收录:
学科分类:1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金:supported by the Federal budget of the INR
主 题:GAN Genetics Giant axonal neuropathy Incapacity Neurodegenerative
摘 要:Background Giant axonal neuropathy (GAN) is a rare neurodegenerative disease transmitted in an autosomal recessive mode. This disorder presents motor and sensitive symptoms with an onset in early childhood. Progressive neurodegeneration makes the patients wheelchair dependent by the end of the second decade of life. Affected individuals do not survive beyond the third decade of life. Molecular analysis has identified mutations in the gene GAN in patients with this disorder. This gene produces a protein called gigaxonin which is presumably involved in protein degradation via the ubiquitin-proteasome system. However, the underlying molecular mechanism is not clearly understood yet. Methods Here we present the fi rst patient from Mexico with clinical data suggesting GAN. Sequencing of the GAN gene was carried out. Changes in the nucleotide sequence were investigated for their possible impact on protein function and structure using the publicly available prediction tools PolyPhen-2 and PANTHER. Results The patient is a compound heterozygous carrying two novel mutations in the GAN gene. The sequence analy-sis revealed two missense mutations in the Kelch repeats domain. In one allele, a CT transition was found in exon 9 at the nucleotide position 55393 (g.55393CT). In the other allele, a transversion GT in exon 11 at the nucleotide position 67471 (g.67471GT) was observed. Both of the bioinformatic tools predicted that these amino acid substitutions would have a negative impact on gigaxonin s function. Conclusion This work provides useful information for health professionals and expands the spectrum of disease-causing mutations in the GAN gene and it is the first documented case in Mexican population.