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Deleterious fibronectin type III-related gene variants may induce a spinal extradural arachnoid cyst: an exome sequencing study of identical twin cases

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Abstract

Purpose

Despite numerous studies, the etiology of spinal extradural arachnoid cyst (SEDAC), a lesion associated with neurological symptoms, remains unknown. In this genomic twin study, we investigated the genetic etiology of SEDACs.

Methods

The subjects were identical twins who developed notably similar SEDACs at the same vertebral level. Accordingly, we performed whole-exome sequencing analyses of genomic material from the twins and their parents using a next-generation sequencer. Additionally, we determined their detailed family history and analyzed the family pedigree.

Results

The pedigree analysis suggested the potential presence of SEDACs in certain family members, indicating a genetic disease. Sequenced data were analyzed and filtered using a purpose-built algorithm, leading to the identification of 155 novel single-nucleotide polymorphisms (SNPs), of which 118 encoded missense or nonsense variants. A functional analysis of the proteins encoded by these SNP alleles revealed strong enrichment for the fibronectin type III (FN3) protein domain (q = 0.00576). Specifically, the data indicated that a missense variant affecting the FN3 protein domain of fibronectin 1 (FN1, p.P969S) can be the causal mutation underlying the SEDACs.

Conclusion

The data suggest that deleterious mutations in fibronectin-related genes may cause SEDACs. In particular, it was suspected that a variant of FN1 may be the cause of the SEDACs in the twin cases studied herein. Detailed studies with a larger number of cases are needed.

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Availability of data and materials

The raw data generated during the current study are not publicly available but are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Funding

This study was supported by a Health and Labor Sciences Research Grant for Research on Rare and Intractable Diseases [Jitsuyoka (Nanbyo)-Ippan-003].

Author information

Authors and Affiliations

  1. Department of Neurosurgery, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-Ku, Tokyo, 157-8535, Japan

    Taijun Hana, Hideki Ogiwara & Nobuhito Morota

  2. Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-Ku, Tokyo, 157-8535, Japan

    Ohsuke Migita, Kazuhiko Nakabayashi & Kenichiro Hata

  3. Department of Pediatrics, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-Ku, Kawasaki, Kanagawa, 216-8511, Japan

    Ohsuke Migita

  4. Department of Neurosurgery, Kitasato University Hospital, 1-15-1 Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0374, Japan

    Nobuhito Morota

Authors
  1. Taijun Hana
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  2. Hideki Ogiwara
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Contributions

T.H. and H.O. designed and performed the research, contributed to the data analysis, and wrote the manuscript. T.H., H.O., and N.M. performed surgery and clinically treated the cases. O.M., K.N., and K.H. analyzed the detailed genetic data with whole-exome sequencing. H.O. and N.M. contributed to discussion, reviewed, and edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Taijun Hana.

Ethics declarations

Ethics approval

All study protocols were approved by the Ethical Committee of the National Center for Child Health and Development (Approval no. 541).

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Cases and members of the family provided written informed consent to participate in the study.

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Cases and members of the family provided written informed consent for publication.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Hana, T., Ogiwara, H., Migita, O. et al. Deleterious fibronectin type III-related gene variants may induce a spinal extradural arachnoid cyst: an exome sequencing study of identical twin cases. Childs Nerv Syst 37, 2329–2334 (2021). https://doi.org/10.1007/s00381-021-05137-4

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  • DOI: https://doi.org/10.1007/s00381-021-05137-4

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