Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 23;12(12):1843.
doi: 10.3390/genes12121843.

Individual Oligogenic Background in p.D91A- SOD1 Amyotrophic Lateral Sclerosis Patients

Giulia Gentile  1 , Benedetta Perrone  2 , Giovanna Morello  1 , Isabella Laura Simone  3 , Sebastiano Andò  2   4 , Sebastiano Cavallaro  1 , Francesca Luisa Conforti  2
Affiliations

Individual Oligogenic Background in p.D91A- SOD1 Amyotrophic Lateral Sclerosis Patients

Giulia Gentile et al. Genes (Basel). .

Abstract

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.

Keywords: NGS targeted-gene panel; individual oligogenic background; p.D91A-SOD1; zygosity.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Workflow of the variant prioritization strategy adopted. The figure was created editing funnels and healthcare infographics provided by https://infograpia.com/, accessed on 12 July 2021.
See this image and copyright information in PMC

References

    1. Renton A.E., Chiò A., Traynor B.J. State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci. 2014;17:17–23. doi: 10.1038/nn.3584. - DOI - PMC - PubMed
    1. Rowland L.P., Shneider N.A. Amyotrophic Lateral Sclerosis. N. Engl. J. Med. 2001;344:1688–1700. doi: 10.1056/NEJM200105313442207. - DOI - PubMed
    1. Bandres-Ciga S., Noyce A.J., Hemani G., Nicolas A., Calvo A., Mora G., Arosio A., Barberis M., Bartolomei I., Battistini S., et al. Shared polygenic risk and causal inferences in amyotrophic lateral sclerosis. Ann. Neurol. 2019;85:470–481. doi: 10.1002/ana.25431. - DOI - PMC - PubMed
    1. Felbecker A., Camu W., Valdmanis P.N., Sperfeld A.D., Waibel S., Steinbach P., Rouleau G.A., Ludolph A.C., Andersen P.M. Four familial ALS pedigrees discordant for two SOD1 mutations: Are all SOD1 mutations pathogenic? J. Neurol. Neurosurg. Psychiatry. 2010;81:572–577. doi: 10.1136/jnnp.2009.192310. - DOI - PubMed
    1. Farrugia Wismayer M., Farrugia Wismayer A., Pace A., Vassallo N., Cauchi R.J. SOD1 D91A variant in the southernmost tip of Europe: A heterozygous ALS patient resident on the island of Gozo. Eur. J. Hum. Genet. 2021;27:27–30. doi: 10.1038/s41431-021-00975-x. - DOI - PMC - PubMed

Publication types