Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations - Sorbonne Université Access content directly
Journal Articles European Journal of Human Genetics Year : 2023

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

Mustafa A Salih
Hassab Elrasoul Siddig
  • Function : Author
Farouk Yassen Omer
  • Function : Author
Sara Emad
  • Function : Author
Isra Z M Eltazi
  • Function : Author
Zulfa Omer
  • Function : Author
Mayada O E Mohamed
  • Function : Author
Ali A Elhassan
Esraa S A Alfadul
Shaimaa Omer M. A. Taha
  • Function : Author
Mutaz Amin
  • Function : Author
Mahmoud Koko
Muntaser E Ibrahim

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. 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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Licence : CC BY - Attribution

Dates and versions

hal-04513649 , version 1 (20-03-2024)

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Ashraf Yahia, Ahlam a A Hamed, Inaam N Mohamed, Maha A Elseed, Mustafa A Salih, et al.. Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations. European Journal of Human Genetics, 2023, ⟨10.1038/s41431-023-01344-6⟩. ⟨hal-04513649⟩
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