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Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations

Yahia, Ashraf LU orcid ; Hamed, Ahlam A.A. ; Mohamed, Inaam N. ; Elseed, Maha A. ; Salih, Mustafa A. ; El-sadig, Sarah M. ; Siddig, Hassab Elrasoul ; Nasreldien, Ali Elsir Musa ; Abdullah, Mohamed Ahmed and Elzubair, Maha , et al. (2024) In European Journal of Human Genetics 32(10). p.1214-1226
Abstract

Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates.... (More)

Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 affected patients from 38 unrelated Sudanese families segregating multiple forms of SCDs. The age-at-onset in our cohort ranged from birth to 35 years; however, most patients manifested childhood-onset diseases (the mean and median ages at onset were 7.5 and 3 years, respectively). We reached the genetic diagnosis in 63% and possibly up to 73% of the studied families when considering variants of unknown significance. Combining the present data with our previous analysis of 25 Sudanese HSP families, the success rate reached 52–59% (31–35/59 families). In this article we report candidate variants in genes previously known to be associated with SCDs or other phenotypically related monogenic disorders. We also highlight the genetic and clinical heterogeneity of SCDs in Sudan, as we did not identify a major causative gene in our cohort, and the potential for discovering novel SCD genes in this population.

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publishing date
type
Contribution to journal
publication status
published
in
European Journal of Human Genetics
volume
32
issue
10
pages
1214 - 1226
publisher
Nature Publishing Group
external identifiers
  • scopus:85151547062
  • pmid:37012327
ISSN
1018-4813
DOI
10.1038/s41431-023-01344-6
language
English
LU publication?
no
additional info
Publisher Copyright: © The Author(s) 2023.
id
ee7915ae-cf29-4eae-9652-e43ff8b87143
date added to LUP
2026-06-05 10:25:36
date last changed
2026-09-27 01:11:54
@article{ee7915ae-cf29-4eae-9652-e43ff8b87143,
  abstract     = {{<p>Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 affected patients from 38 unrelated Sudanese families segregating multiple forms of SCDs. The age-at-onset in our cohort ranged from birth to 35 years; however, most patients manifested childhood-onset diseases (the mean and median ages at onset were 7.5 and 3 years, respectively). We reached the genetic diagnosis in 63% and possibly up to 73% of the studied families when considering variants of unknown significance. Combining the present data with our previous analysis of 25 Sudanese HSP families, the success rate reached 52–59% (31–35/59 families). In this article we report candidate variants in genes previously known to be associated with SCDs or other phenotypically related monogenic disorders. We also highlight the genetic and clinical heterogeneity of SCDs in Sudan, as we did not identify a major causative gene in our cohort, and the potential for discovering novel SCD genes in this population.</p>}},
  author       = {{Yahia, Ashraf and Hamed, Ahlam A.A. and Mohamed, Inaam N. and Elseed, Maha A. and Salih, Mustafa A. and El-sadig, Sarah M. and Siddig, Hassab Elrasoul and Nasreldien, Ali Elsir Musa and Abdullah, Mohamed Ahmed and Elzubair, Maha and Omer, Farouk Yassen and Bakhiet, Aisha Motwakil and Abubaker, Rayan and Abozar, Fatima and Adil, Rawaa and Emad, Sara and Musallam, Mhammed Alhassan and Eltazi, Isra Z.M. and Omer, Zulfa and Malik, Hiba and Mohamed, Mayada O.E. and Elhassan, Ali A. and Mohamed, Eman O.E. and Ahmed, Ahmed K.M.A. and Ahmed, Elhami A.A. and Eltaraifee, Esraa and Hussein, Bidour K. and Abd Allah, Amal S.I. and Salah, Lina and Nimir, Mohamed and Tag Elseed, Omnia M. and Elhassan, Tasneem E.A. and Elbashier, Abubakr and Alfadul, Esraa S.A. and Fadul, Moneeb and Ali, Khalil F. and Taha, Shaimaa Omer M.A. and Bushara, Elfatih E. and Amin, Mutaz and Koko, Mahmoud and Ibrahim, Muntaser E. and Ahmed, Ammar E. and Elsayed, Liena E.O. and Stevanin, Giovanni}},
  issn         = {{1018-4813}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{1214--1226}},
  publisher    = {{Nature Publishing Group}},
  series       = {{European Journal of Human Genetics}},
  title        = {{Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations}},
  url          = {{http://dx.doi.org/10.1038/s41431-023-01344-6}},
  doi          = {{10.1038/s41431-023-01344-6}},
  volume       = {{32}},
  year         = {{2024}},
}