Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases
Abstract Genetic neuromuscular diseases are clinically and genetically heterogeneous genetic disorders that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study aimed to identify pathogenic variants, calculate carrier frequency, and predict the genetic prevalence...
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Nature Portfolio
2024-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-54413-1 |
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| author | Won-Jun Choi Soo-Hyun Kim Sung Rok Lee Seung-Hun Oh Seung Woo Kim Ha Young Shin Hyung Jun Park |
| author_facet | Won-Jun Choi Soo-Hyun Kim Sung Rok Lee Seung-Hun Oh Seung Woo Kim Ha Young Shin Hyung Jun Park |
| author_sort | Won-Jun Choi |
| collection | DOAJ |
| description | Abstract Genetic neuromuscular diseases are clinically and genetically heterogeneous genetic disorders that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study aimed to identify pathogenic variants, calculate carrier frequency, and predict the genetic prevalence of autosomal recessive neuromuscular diseases (AR-NMDs). We selected 268 AR-NMD genes and analyzed their genetic variants sourced from the gnomAD database. After identifying the pathogenic variants using an algorithm, we calculated the carrier frequency and predicted the genetic prevalence of AR-NMDs. In total, 10,887 pathogenic variants were identified, including 3848 literature verified and 7039 manually verified variants. In the global population, the carrier frequency of AR-NMDs is 32.9%, with variations across subpopulations ranging from 22.4% in the Finnish population to 36.2% in the non-Finnish European population. The predicted genetic prevalence of AR-NMDs was estimated to be 24.3 cases per 100,000 individuals worldwide, with variations across subpopulations ranging from 26.5 to 41.4 cases per 100,000 individuals in the Latino/Admixed American and the Ashkenazi Jewish populations, respectively. The AR-NMD gene with the highest carrier frequency was GAA (1.3%) and the variant with the highest allele frequency was c.-32-13 T>G in GAA with 0.0033 in the global population. Our study revealed a higher-than-expected frequency of AR-NMD carriers, constituting approximately one-third of the global population, highlighting ethnic heterogeneity in genetic susceptibility. |
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| language | English |
| last_indexed | 2024-03-07T15:02:22Z |
| publishDate | 2024-02-01 |
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| spelling | doaj.art-72f62adbc24f4894bb9c4c6e2cb9fabd2024-03-05T19:04:15ZengNature PortfolioScientific Reports2045-23222024-02-011411910.1038/s41598-024-54413-1Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseasesWon-Jun Choi0Soo-Hyun Kim1Sung Rok Lee2Seung-Hun Oh3Seung Woo Kim4Ha Young Shin5Hyung Jun Park6CHA University School of MedicineDepartment of Neurology, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Neurology, Gangnam Severance Hospital, Yonsei University College of MedicineDepartment of Neurology, CHA Bundang Medical Center, CHA UniversityDepartment of Neurology, Severance Hospital, Yonsei University College of MedicineDepartment of Neurology, Severance Hospital, Yonsei University College of MedicineDepartment of Neurology, Gangnam Severance Hospital, Yonsei University College of MedicineAbstract Genetic neuromuscular diseases are clinically and genetically heterogeneous genetic disorders that primarily affect the peripheral nerves, muscles, and neuromuscular junctions. This study aimed to identify pathogenic variants, calculate carrier frequency, and predict the genetic prevalence of autosomal recessive neuromuscular diseases (AR-NMDs). We selected 268 AR-NMD genes and analyzed their genetic variants sourced from the gnomAD database. After identifying the pathogenic variants using an algorithm, we calculated the carrier frequency and predicted the genetic prevalence of AR-NMDs. In total, 10,887 pathogenic variants were identified, including 3848 literature verified and 7039 manually verified variants. In the global population, the carrier frequency of AR-NMDs is 32.9%, with variations across subpopulations ranging from 22.4% in the Finnish population to 36.2% in the non-Finnish European population. The predicted genetic prevalence of AR-NMDs was estimated to be 24.3 cases per 100,000 individuals worldwide, with variations across subpopulations ranging from 26.5 to 41.4 cases per 100,000 individuals in the Latino/Admixed American and the Ashkenazi Jewish populations, respectively. The AR-NMD gene with the highest carrier frequency was GAA (1.3%) and the variant with the highest allele frequency was c.-32-13 T>G in GAA with 0.0033 in the global population. Our study revealed a higher-than-expected frequency of AR-NMD carriers, constituting approximately one-third of the global population, highlighting ethnic heterogeneity in genetic susceptibility.https://doi.org/10.1038/s41598-024-54413-1Genetic prevalenceCarrier frequencyGenomeHumanNeuromuscular diseasePathogenic variant |
| spellingShingle | Won-Jun Choi Soo-Hyun Kim Sung Rok Lee Seung-Hun Oh Seung Woo Kim Ha Young Shin Hyung Jun Park Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases Scientific Reports Genetic prevalence Carrier frequency Genome Human Neuromuscular disease Pathogenic variant |
| title | Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases |
| title_full | Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases |
| title_fullStr | Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases |
| title_full_unstemmed | Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases |
| title_short | Global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases |
| title_sort | global carrier frequency and predicted genetic prevalence of patients with pathogenic sequence variants in autosomal recessive genetic neuromuscular diseases |
| topic | Genetic prevalence Carrier frequency Genome Human Neuromuscular disease Pathogenic variant |
| url | https://doi.org/10.1038/s41598-024-54413-1 |
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