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Histopathology of recurrent Steel syndrome in fetuses caused by novel variants of COL27A1 gene

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Abstract

Steel syndrome (STLS) encompasses characteristic facies, dwarfness, irreducible bilateral hip and radial head dislocation, and carpal bone coalition due to COL27A1 mutations. Two consecutive pregnancies in a non-consanguineous couple were terminated because of severe fetal anomalies. Complete autopsies with microscopic exam were performed on both fetuses. Next-generation-based clinical exome sequencing was applied to the first fetus. Exome sequencing results, parental segregation, and affection of the second fetus were confirmed by Sanger sequencing. Both fetuses had signs consistent with STLS. Bilateral capitulum humeri absence explained radial head dislocation in STLS. Metaphyseal cartilage showed severe disorganization. Resting cartilage was hypercellular, organized in irregular nests limited by acellular matrix. Two variants in COL27A1 (c.2548G>A -p.Gly850Arg- and c.3249+1G> T) were found in both fetuses in compound heterozygosity with parental Mendelian segregation. This is the first report to include histology of STLS. The COL27A1 variants here described increase the number of mutations associated with STLS.

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Funding

This study was partly supported by grant from Fondo de Investigaciones Sanitarias (grant number PI17/01153), Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Spain.

Author information

Authors and Affiliations

  1. Pathology Department, Hospital Clínic, Barcelona, Spain

    Gerard Frigola & Alfons Nadal

  2. BCNatal, Hospital Clinic, University of Barcelona, Barcelona, Spain

    Olga Gómez del Rincón, Virginia Borobio Florián & Antoni Borrell

  3. qGenomics, Esplugues de Llobregat, Barcelona, Spain

    Anna Vallmajó Fita, Berta Campos & Maria Segura Puimedon

  4. BCNatal, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Montse Pauta

  5. Molecular Biology of Reproduction and Development Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Rafael Oliva

  6. Genetics Unit, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

    Rafael Oliva

  7. Genetics Section, Biochemistry and Molecular Genetics Service, Hospital Clínic, Barcelona, Spain

    Rafael Oliva

  8. Department of Basic Clinical Practice, University of Barcelona, Barcelona, Spain

    Alfons Nadal

  9. Molecular Pathology of Inflammatory Conditions and Solid Tumors Research Group, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Alfons Nadal

Authors
  1. Gerard Frigola
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  2. Olga Gómez del Rincón
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  3. Virginia Borobio Florián
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  4. Anna Vallmajó Fita
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  5. Berta Campos
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  6. Montse Pauta
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  7. Maria Segura Puimedon
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  8. Rafael Oliva
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  9. Antoni Borrell
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  10. Alfons Nadal
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Contributions

Gerard Frigola contributed to data acquisition, data analysis, and manuscript redaction.

Olga Gómez del Rincón contributed to data acquisition.

Virginia Borobio Florián contributed to data acquisition.

Anna Vallmajó Fita contributed to data acquisition and data analysis.

Berta Campos contributed to data acquisition, data analysis, and manuscript redaction.

Montse Pauta contributed to data analysis.

Maria Segura Puimedon contributed to data analysis and manuscript redaction.

Rafael Oliva contributed to data acquisition and manuscript redaction.

Antoni Borrell contributed to data analysis and manuscript redaction.

Alfons Nadal contributed to data acquisition, data analysis, and manuscript redaction.

All authors have read, contributed, and approved the final version of the manuscript.

Corresponding author

Correspondence to Alfons Nadal.

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Research involving human or animal participants

This article does not contain any research studies with human participants or animals performed by any of the authors.

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Informed consent was obtained for all performed procedures

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Frigola, G., del Rincón, O.G., Florián, V.B. et al. Histopathology of recurrent Steel syndrome in fetuses caused by novel variants of COL27A1 gene. Virchows Arch 479, 413–418 (2021). https://doi.org/10.1007/s00428-020-02979-2

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  • DOI: https://doi.org/10.1007/s00428-020-02979-2

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