A novel mutation in the ALS2 gene in an Iranian Kurdish family with Juvenile amyotrophic lateral sclerosis
A novel mutation in the ALS2 gene in an Iranian Kurdish family with Juvenile amyotrophic lateral sclerosis
Yousef Daneshmandpour,1,*Zahra Bahmanpour,2Somayeh Kazeminasab,3Hossein Darvish,4Babak Emamalizadeh,5
1. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 4. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 5. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
Introduction: Amyotrophic lateral sclerosis (ALS) is a rare pediatrics disorder that affects both upper and lower motor neurons. Global muscle loss, muscle weakness, and respiratory involvement are observed in ALS patients. Both environmental and genetic factors are involved in ALS etiology. Mutations in Alsin Rho Guanine Nucleotide Exchange Factor (ALS2) correlates with three similar but distinctive syndromes, including the juvenile form of ALS.
Methods: An Iranian Kurdish family was involved in this study and all members were evaluated with relevant clinical guidelines. Whole exome sequencing (WES) and sanger sequencing were applied to all family members to undermine the possible genetic factors. Using online bioinformatics tools, the effect of the identified mutation on 3D structure and function of protein was studied.
Results: A substitution c. 2110 C>T (p. Arg704X) identified in the ALS2 gene. Bioinformatics analysis showed the mutation is located in the well-conserved and functional domain of the protein.
Conclusion: This study recognized a novel mutation in the ALS2 gene in a proband with the juvenile form of ALS. Alignment analysis represented that the sequence of the ALS2 is well conserved among similar species and humans, implying its potential vital role in proper cell function. Other members of the ALS2 protein interaction network are reported to correlate in ALS etiology. The altered folding of the mutant Superoxide dismutase 1 (SOD1) is reported in ALS and its aggregation is related to the onset and progression of ALS. Also, a higher level of soluble SOD1 in the nucleus results in a longer disease duration To our knowledge, this is the first identified ALS2 mutation among the Iranian population. Screening of ALS2 would be a helpful diagnostic strategy in patients with similar phenotypes