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Cytogenetics and Molecular Genetics

The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman syndrome

Leukemia volume 23, pages 708–711 (2009)Cite this article

Abstract

Shwachman–Diamond syndrome (SDS) is an autosomal recessive disorder, characterized by exocrine pancreatic insufficiency, skeletal abnormalities and bone marrow (BM) dysfunction with an increased risk to develop myelodysplastic syndrome and/or acute myeloid leukaemia (MDS/AML). SDS is caused, in nearly 90% of cases, by two common mutations (that is, c.183_184TA>CT and c.258+2T>C) in exon 2 of the SBDS gene, localized on chromosome 7. Clonal chromosome anomalies are often found in the BM of SDS patients; the most frequent is an isochromosome for long arms of chromosome 7, i(7)(q10). We studied eight patients with SDS carrying the i(7)(q10) who were compound heterozygotes for SBDS mutations. By assessing the parental origin of the i(7)(q10) using microsatellite analysis, we inferred from the results which mutation was present in double dose in the isochromosome. We demonstrate that in all cases the i(7)(q10) carries a double dose of the c.258+2T>C, and we suggest that, as the c.258+2T>C mutation still allows the production of some amount of normal protein, this may contribute to the low incidence of MDS/AML in this subset of SDS patients.

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Acknowledgements

This study was partially supported by grants from AISS (Associazione Italiana Sindrome di Shwachman) and from MIUR (Ministero dell’Istruzione, Università e della Ricerca)––PRIN 2006065440. This study was carried out at Università di Pavia, Università di Varese, University Hospital of Verona. AM performed mutation analysis and worked on establishing parental origin, EM performed cytogenetics and EN performed mutation analysis and RNA studies.

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Author notes

  1. A Minelli, E Maserati and E Nicolis: These three authors contributed equally to this work.

Authors and Affiliations

  1. Genetica Medica, Fondazione IRCCS Policlinico San Matteo Università di Pavia e, Pavia, Italy

    A Minelli, E De Paoli & C Danesino

  2. Dipartimento Scienze Biomediche Sperimentali e Cliniche, Università dell’Insubria, Varese, Italy

    E Maserati, F Lo Curto & F Pasquali

  3. Laboratory of Molecular Pathology, Laboratory of Clinical Chemistry and Haematology, University Hospital of Verona, Verona, Italy

    E Nicolis

  4. Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Università di Pavia, Pavia, Italy

    M Zecca & F Locatelli

  5. Clinica di Oncoematologia Pediatrica, Università di Padova, Padova, Italy

    L Sainati

  6. Clinica Pediatrica Università Milano-Bicocca, OC San Gerardo, Monza, Italy

    D Longoni

  7. Dipartimento di Oncologia AORN Santobono Pausilipon, Napoli, Italy

    G Menna

  8. Clinica Pediatrica IRCCS Burlo Garofolo, Università di Trieste, Trieste, Italy

    F Poli

  9. Cystic Fibrosis Center, Verona, Italy

    M Cipolli

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  1. A Minelli
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  2. E Maserati
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  3. E Nicolis
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  10. E De Paoli
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  11. M Cipolli
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Corresponding author

Correspondence to C Danesino.

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Minelli, A., Maserati, E., Nicolis, E. et al. The isochromosome i(7)(q10) carrying c.258+2t>c mutation of the SBDS gene does not promote development of myeloid malignancies in patients with Shwachman syndrome. Leukemia 23, 708–711 (2009). https://doi.org/10.1038/leu.2008.369

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