期刊
GENES
卷 12, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/genes12121843
关键词
p; D91A-SOD1; zygosity; NGS targeted-gene panel; individual oligogenic background
资金
- Italian Ministry of Education, University and Research (MIUR)
- MIUR [CTN01_00177_817708]
- European Social Fund operational program for the Sicily region (Italy) Development and application of biosensoristic technologies in genomics PO FESR Sicily 2014-2020 grant
- MIUR
The presence of unique sets of variants in p.D91A-SOD1 ALS patients suggests the importance of individual oligogenic background in disease progression. Comprehensive genomic observations may enhance disease diagnosis accuracy and guide the advancement of precision medicine.
The p.D91A is one of the most common ALS-causing SOD1 mutations and is known to be either recessive or dominant. The homozygous phenotype is characterized by prolonged survival and slow progression of disease, whereas the affected heterozygous phenotypes can vary. To date, no genetic protective factors located close to SOD1 have been associated with the mild progressive homozygous phenotype. Using Next Generation Sequencing (NGS), we characterized a small cohort of sporadic and familial p.D91A-SOD1 heterozygous (n = 2) or homozygous (n = 5) ALS patients, to reveal any additional contributing variant in 39 ALS-related genes. We detected unique sets of non-synonymous variants, four of which were of uncertain significance and several in untranslated regions of ALS-related genes. Our results supported an individual oligogenic background underlying both sporadic and familial p.D91A cases irrespective of their p.D91A mutant alleles. We suggest that a comprehensive genomic view of p.D91A-SOD1 ALS patients may be useful in identifying emerging variants and improving disease diagnosis as well as guiding precision medicine.
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