A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans
| dc.contributor.author | Mahungu, Amokelani C | |
| dc.contributor.author | Monnakgotla, Nomakhosazana | |
| dc.contributor.author | Nel, Melissa | |
| dc.contributor.author | Heckmann, Jeannine M | |
| dc.date.accessioned | 2022-04-13T09:50:04Z | |
| dc.date.available | 2022-04-13T09:50:04Z | |
| dc.date.issued | 2022-03-24 | |
| dc.date.updated | 2022-03-27T03:10:27Z | |
| dc.description.abstract | Background Genetic investigations of inherited neuromuscular disorders in Africans, have been neglected. We aimed to summarise the published data and comment on the genetic evidence related to inherited neuropathies (Charcot-Marie-Tooth disease (CMT)), hereditary spastic paraplegias (HSP) and spinal muscular atrophy (SMA) in Africans. Methods PubMed was searched for relevant articles and manual checking of references and review publications were performed for African-ancestry participants with relevant phenotypes and identified genetic variants. For each case report we extracted phenotype information, inheritance pattern, variant segregation and variant frequency in population controls (including up to date frequencies from the gnomAD database). Results For HSP, 23 reports were found spanning the years 2000–2019 of which 19 related to North Africans, with high consanguinity, and six included sub-Saharan Africans. For CMT, 19 reports spanning years 2002–2021, of which 16 related to North Africans and 3 to sub-Saharan Africans. Most genetic variants had not been previously reported. There were 12 reports spanning years 1999–2020 related to SMN1-SMA caused by homozygous exon 7 ± 8 deletion. Interestingly, the population frequency of heterozygous SMN1-exon 7 deletion mutations appeared 2 × lower in Africans compared to Europeans, in addition to differences in the architecture of the SMN2 locus which may impact SMN1-SMA prognosis. Conclusions Overall, genetic data on inherited neuromuscular diseases in sub-Saharan Africa, are sparse. If African patients with rare neuromuscular diseases are to benefit from the expansion in genomics capabilities and therapeutic advancements, then it is critical to document the mutational spectrum of inherited neuromuscular disease in Africa. Highlights Review of genetic variants reported in hereditary spastic paraplegia in Africans Review of genetic variants reported in genetic neuropathies in Africans Review of genetic underpinnings of spinal muscular atrophies in Africans Assessment of pathogenic evidence for candidate variants | en_US |
| dc.identifier.apacitation | Mahungu, A. C., Monnakgotla, N., Nel, M., & Heckmann, J. M. (2022). A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans. <i>Orphanet Journal of Rare Diseases</i>, 17(1), 133. http://hdl.handle.net/11427/36371 | en_ZA |
| dc.identifier.chicagocitation | Mahungu, Amokelani C, Nomakhosazana Monnakgotla, Melissa Nel, and Jeannine M Heckmann "A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans." <i>Orphanet Journal of Rare Diseases</i> 17, 1. (2022): 133. http://hdl.handle.net/11427/36371 | en_ZA |
| dc.identifier.citation | Mahungu, A.C., Monnakgotla, N., Nel, M. & Heckmann, J.M. 2022. A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans. <i>Orphanet Journal of Rare Diseases.</i> 17(1):133. http://hdl.handle.net/11427/36371 | en_ZA |
| dc.identifier.ris | TY - Journal Article AU - Mahungu, Amokelani C AU - Monnakgotla, Nomakhosazana AU - Nel, Melissa AU - Heckmann, Jeannine M AB - Background Genetic investigations of inherited neuromuscular disorders in Africans, have been neglected. We aimed to summarise the published data and comment on the genetic evidence related to inherited neuropathies (Charcot-Marie-Tooth disease (CMT)), hereditary spastic paraplegias (HSP) and spinal muscular atrophy (SMA) in Africans. Methods PubMed was searched for relevant articles and manual checking of references and review publications were performed for African-ancestry participants with relevant phenotypes and identified genetic variants. For each case report we extracted phenotype information, inheritance pattern, variant segregation and variant frequency in population controls (including up to date frequencies from the gnomAD database). Results For HSP, 23 reports were found spanning the years 2000–2019 of which 19 related to North Africans, with high consanguinity, and six included sub-Saharan Africans. For CMT, 19 reports spanning years 2002–2021, of which 16 related to North Africans and 3 to sub-Saharan Africans. Most genetic variants had not been previously reported. There were 12 reports spanning years 1999–2020 related to SMN1-SMA caused by homozygous exon 7 ± 8 deletion. Interestingly, the population frequency of heterozygous SMN1-exon 7 deletion mutations appeared 2 × lower in Africans compared to Europeans, in addition to differences in the architecture of the SMN2 locus which may impact SMN1-SMA prognosis. Conclusions Overall, genetic data on inherited neuromuscular diseases in sub-Saharan Africa, are sparse. If African patients with rare neuromuscular diseases are to benefit from the expansion in genomics capabilities and therapeutic advancements, then it is critical to document the mutational spectrum of inherited neuromuscular disease in Africa. Highlights Review of genetic variants reported in hereditary spastic paraplegia in Africans Review of genetic variants reported in genetic neuropathies in Africans Review of genetic underpinnings of spinal muscular atrophies in Africans Assessment of pathogenic evidence for candidate variants DA - 2022-03-24 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Orphanet Journal of Rare Diseases KW - Hereditary spastic paraplegia KW - Genetic neuropathies KW - Charcot Marie Tooth disease KW - CMT KW - Spinal Muscular Atrophy KW - Africa KW - Inherited neuromuscular disorders LK - https://open.uct.ac.za PY - 2022 T1 - A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans TI - A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans UR - http://hdl.handle.net/11427/36371 ER - | en_ZA |
| dc.identifier.uri | https://doi.org/10.1186/s13023-022-02280-2 | |
| dc.identifier.uri | http://hdl.handle.net/11427/36371 | |
| dc.identifier.vancouvercitation | Mahungu AC, Monnakgotla N, Nel M, Heckmann JM. A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans. Orphanet Journal of Rare Diseases. 2022;17(1):133. http://hdl.handle.net/11427/36371. | en_ZA |
| dc.language.iso | en | en_US |
| dc.language.rfc3066 | en | |
| dc.publisher.department | Department of Medicine | en_US |
| dc.publisher.faculty | Faculty of Health Sciences | en_US |
| dc.rights.holder | The Author(s) | |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
| dc.source | Orphanet Journal of Rare Diseases | en_US |
| dc.source.journalissue | 1 | en_US |
| dc.source.journalvolume | 17 | en_US |
| dc.source.pagination | 133 | en_US |
| dc.subject | Hereditary spastic paraplegia | en_US |
| dc.subject | Genetic neuropathies | en_US |
| dc.subject | Charcot Marie Tooth disease | en_US |
| dc.subject | CMT | en_US |
| dc.subject | Spinal Muscular Atrophy | en_US |
| dc.subject | Africa | en_US |
| dc.subject | Inherited neuromuscular disorders | en_US |
| dc.title | A review of the genetic spectrum of hereditary spastic paraplegias, inherited neuropathies and spinal muscular atrophies in Africans | en_US |
| dc.type | Journal Article | en_US |