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Novel ERLIN2 variant expands the phenotype of Spastic Paraplegia 18

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Abstract

Background

The Brazilian Northeast region is notable for its high prevalence of consanguineous marriages and isolated populations, which has led to a significant prevalence of rare genetic disorders. This study describes the clinical presentation of four affected individuals from the same family, comprising two siblings and their cousins, with ages ranging from 11 to 20 years.

Methods

In a small and isolated community in Northeastern Brazil, affected individuals initially underwent a clinical assessment. Subsequently, written consent was obtained from their legal guardians, and an extensive clinical evaluation was conducted at a medical genetics center. Family data provided the basis for constructing the pedigree, and biological samples (blood or oral swabs) were collected from both affected and unaffected family members. Following informed consent from one patient, Whole Exome Sequencing (WES) was carried out, encompassing exome sequencing, assembly, genotyping, and annotation. A potentially deleterious variant was then singled out for further segregation analysis through Sanger Sequencing, involving both the proband and select family members.

Results and conclusion

These individuals exhibit severe neurodevelopmental delays, encompassing symptoms such as spastic paraplegia, neuropathy, intellectual impairments, and language challenges. Through next-generation sequencing (NGS) techniques, a previously unreported homozygous variant within the ERLIN2 gene linked to spastic paraplegia 18 (SPG18) was identified across all four patients. Also, all patients displayed childhood cataract, expanding the known clinical spectrum of SPG18.

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Data availability

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to personal identifying information.

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Acknowledgements

The authors wish to thank the patients and their family members for participation in this study.

Funding

This research was funded by the Research Program for the Unified Health System (PPSUS): shared management in health (Process Number: 60030.0000000215/2021).

Author information

Authors and Affiliations

  1. Medical Genetics Sector, Faculty of Medicine, Federal University of Alagoas, Maceió, Alagoas, Brazil

    Guilherme Carvalho de Souza, Maria Carolina Malta, Mirele Raíssa Silva Santos & Thalita Figueiredo

  2. Clinical Genetics Service, Medical Genetics Sector, Faculty of Medicine, University Hospital, Federal University of Alagoas, Maceió, Alagoas, Brazil

    Marshall Ítalo Barros Fontes

  3. Center of Health Sciences, Alagoas State University of Health Sciences-UNCISAL, Maceió, Alagoas, Brazil

    Marshall Ítalo Barros Fontes

  4. Ophthalmology Sector, Faculty of Medicine, University Hospital, Federal University of Alagoas, Maceió, Alagoas, Brazil

    Juliana Lopes de Sousa Anjos & Diego Patrício Ribeiro

  5. Child Neurology Service, Department of Neurology, University of São Paulo School of Medicine, São Paulo, SP, Brazil

    Fernando Kok

  6. Mendelics Genomic Analysis, São Paulo, SP, Brazil

    Fernando Kok

Authors
  1. Guilherme Carvalho de Souza
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  2. Maria Carolina Malta
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  3. Mirele Raíssa Silva Santos
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  4. Marshall Ítalo Barros Fontes
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  5. Juliana Lopes de Sousa Anjos
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  6. Diego Patrício Ribeiro
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  7. Fernando Kok
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  8. Thalita Figueiredo
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Contributions

Conceptualization, T.F.; methodology, T.F. and F.K..; investigation, T.F., F.K., G.S., M.M., M.S., M.F., J.A. and D.R.; writing—original draft preparation, T.F., G.S., M.M. and M.S..; writing—review and editing, all authors; supervision, T.F.; project administration, T.F.; funding acquisition, T.F. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Thalita Figueiredo.

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Competing interests

Fernando Kok is a shareholder and Medical Director of Mendelics Genomic Analysis and Associated Editor for Neurogenetics of Arquivos de Neuropsiquiatria.

Ethics approval and consent to participate

The data sampling protocol, as well as the consent procedure, were analyzed and approved by the National Research Ethics Committee—CONEP (Process 39674220.1.1001.5013).

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de Souza, G.C., Malta, M.C., Santos, M.R.S. et al. Novel ERLIN2 variant expands the phenotype of Spastic Paraplegia 18. Neurol Sci 45, 2705–2710 (2024). https://doi.org/10.1007/s10072-023-07271-0

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  • DOI: https://doi.org/10.1007/s10072-023-07271-0

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