<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized by progressive degeneration of the upper and lower motor neurons, leading to muscle weakness, hypotrophy, swallowing and respiratory failure. The cause of ALS is not yet fully elucidated, but there are 35 associated genes and 2 gene loci with an unidentified gene. The most common are C9orf72, SOD1, TARDBP and FUS found in approximately 10% of patients. Variants in the C9orf72 gene are the main cause of fALS – 25-40% of cases (and a small percentage of sALS). The goal of the present study was to evaluate the significance of the C9orf72 hexanucleotide repeat expansion in Bulgarian patients with ALS, through the means of in house and triplet repeat-primed PCR assay (TP-PCR). From 171 patients diagnosed with ALS and included in the current study, we have identified the repeat expansion with more than 145 GGGGCC repeats in 7 (4,1%). Short expansions or borderline values (24 to 30 repeats) were not detected. Due to absence of sufficient data, we have established an ALS-focused research for the association of the C9orf72 gene in clinically well-characterized Bulgarian ALS patients. Published data show variable percentage ratios for genetically verified cases (4-40%), which is mainly due to small sample counts and sALS-fALS ratios. Our patients’ group also contains sALS and fALS cases, which explains the low percentage of genetic verification. The obtained results enrich the worldwide database and shed light onto genetically characterized Bulgarian ALS patients. Affected patients and their families can receive adequate medical-genetic consultation and prenatal diagnostic testing.</p>
</abstract>

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized by progressive degeneration of the upper and lower motor neurons, leading to muscle weakness, hypotrophy, swallowing and respiratory failure. The cause of ALS is not yet fully elucidated, but there are 35 associated genes and 2 gene loci with an unidentified gene. The most common are C9orf72, SOD1, TARDBP and FUS found in approximately 10% of patients. Variants in the C9orf72 gene are the main cause of fALS – 25-40% of cases (and a small percentage of sALS). The goal of the present study was to evaluate the significance of the C9orf72 hexanucleotide repeat expansion in Bulgarian patients with ALS, through the means of in house and triplet repeat-primed PCR assay (TP-PCR). From 171 patients diagnosed with ALS and included in the current study, we have identified the repeat expansion with more than 145 GGGGCC repeats in 7 (4,1%). Short expansions or borderline values (24 to 30 repeats) were not detected. Due to absence of sufficient data, we have established an ALS-focused research for the association of the C9orf72 gene in clinically well-characterized Bulgarian ALS patients. Published data show variable percentage ratios for genetically verified cases (4-40%), which is mainly due to small sample counts and sALS-fALS ratios. Our patients’ group also contains sALS and fALS cases, which explains the low percentage of genetic verification. The obtained results enrich the worldwide database and shed light onto genetically characterized Bulgarian ALS patients. Affected patients and their families can receive adequate medical-genetic consultation and prenatal diagnostic testing.

Targeted Screening of the <italic>C9orf72</italic> Gene in Bulgarian Amyotrophic Lateral Sclerosis Patients

Genetic Medico-Diagnostic Laboratory “Genica” – Sofia

University Hospital Aleksandrovska, Medical University – Sofia

Department of Medical Chemistry and Biochemistry

Department of Cognitive Science and Psychology

Acta Medica Bulgarica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Targeted Screening of the  Gene in Bulgarian Amyotrophic Lateral Sclerosis Patients

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, characterized by progressive degeneration of the upper and lower motor neurons, leading to...

Targeted Screening of the C9orf72 Gene in Bulgarian Amyotrophic Lateral Sclerosis Patients

Published Online: Apr 22, 2022

Page range: 12 - 16

Received: Nov 04, 2021

Accepted: Dec 11, 2021

DOI: https://doi.org/10.2478/amb-2022-0002

Keywords
amyotrophic lateral sclerosis, C9orf72 gene, hexanucleotide repeat expansion

© 2022 S. Ormandzhiev et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Targeted Screening of the C9orf72 Gene in Bulgarian Amyotrophic Lateral Sclerosis Patients

Published Online: Apr 22, 2022

Page range: 12 - 16

Received: Nov 04, 2021

Accepted: Dec 11, 2021

DOI: https://doi.org/10.2478/amb-2022-0002

Keywordsamyotrophic lateral sclerosis, C9orf72 gene, hexanucleotide repeat expansion

© 2022 S. Ormandzhiev et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Keywords
amyotrophic lateral sclerosis, C9orf72 gene, hexanucleotide repeat expansion