Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Valuable insights into hereditary spinocerebellar degeneration from clusters of homozygosity in Africa

European Journal of Human Genetics (2023)Cite this article

Subjects

The Original Article was published on 03 April 2023

From its Greek roots, the concept of ataxia derives from the prefix “a-” for “not or without” and the noun “taxis “ for “arrangement or order,” or “tassein” = tactics. This concept is used to describe a clinical presentation that includes altered coordination, balance, and speech. The primary underlying pathophysiology is a degeneration of nerves in the cerebellum (cerebellar degeneration). The degeneration may also involve the spinal cord (spinocerebellar degeneration). Ataxia may be acquired due to environmental exposure such as long-term alcohol abuse, intake of some medications, exposure to some toxins, autoimmune disorders, traumatic injuries of the cerebellum, and infections (including infections to Covid-19). The ataxic syndrome may result from hereditary genetic defects (Hereditary spinocerebellar degeneration, HSCD).

In this issue of the European Journal of Human Genetics, Yahia et al. present a comprehensive study of HSCD in Sudan [1]. The country is a mix of (1°) heterogeneous cultural groups with (2°) clusters of high consanguinity rates. The authors recruited 90 patients with spinocerebellar degenerative disorders from 38 families. Four of these families were unsolved in a previous study targeting SPG57. The authors employed clinical assessment and multiple genetic testing approaches to identify the clinical manifestations and uncover the underlying genetic defects causing spinocerebellar degenerative disorders in those 38 families. The age of onset was very young for the majority of patients (median age of onset three years). The result of the clinical evaluation indicated that limb manifestations were present in both upper and lower limbs in most of the patients. Skeletal deformities, intellectual impairment, developmental delay or regression, and sphincteric disturbances were each observed in more than 20% of patients. Analyzing known HSCD genes resulted in a definite molecular diagnosis in 63% of families (28/38), with 10% more that could be added should putative candidate variants (Variants of Uncertain Significance (VUS)) be upgraded in the future. The mode of inheritance was autosomal recessive homozygous in 75% of solved families. The rate of definite diagnoses in this study is higher than in studies using NGS in traditionally non-consanguineous populations [2].

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: PubMed records for HSCD entities in the World and in Africa (accession date August 1, 2023).

References

  1. Yahia A, Hamed AAA, Mohamed IN, Elseed MA, Salih MA, El-Sadig SM, et al. Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations. Eur J Hum Genet. 2023. https://doi.org/10.1038/s41431-023-01344-6. Online ahead of print.

  2. Jiao B, Zhou Z, Hu Z, Du J, Liao X, Luo Y, et al. Homozygosity mapping and next generation sequencing for the genetic diagnosis of hereditary ataxia and spastic paraplegia in consanguineous families. Parkinsonism Relat Disord. 2020;80:65–72.

    Article  PubMed  Google Scholar 

  3. Ngo KJ, Rexach JE, Lee H, Petty LE, Perlman S, Valera JM, et al. A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders. Hum Mutat. 2020;41:487–501.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

There was no specific funding.

Author information

Authors and Affiliations

  1. Center for Human Genetics, Centre Hospitalier Universitaire, Liège, 4032, Belgium

    Aimé Lumaka

  2. Center for Human Genetics, University of Kinshasa, Kinshasa, Democratic Republic of Congo

    Aimé Lumaka

Authors
  1. Aimé Lumaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aimé Lumaka.

Ethics declarations

Competing interests

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lumaka, A. Valuable insights into hereditary spinocerebellar degeneration from clusters of homozygosity in Africa. Eur J Hum Genet (2023). https://doi.org/10.1038/s41431-023-01452-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41431-023-01452-3

Search

Advanced search

Quick links