title: Shwachman syndrome as mutator phenotype responsible for myeloid dysplasia/neoplasia through karyotype instability and chromosomes 7 and 20 anomalies.
abstract: An investigation of 14 patients with Shwachman syndrome (SS), using standard and molecular cytogenetic methods and molecular genetic techniques, showed that (1) the i(7)(q10) is not, or not always, an isochromosome but may arise from a more complex mechanism, retaining part of the short arm; (2) the i(7)(q10) has no preferential parental origin; (3) clonal chromosome changes, such as chromosome 7 anomalies and del(20)(q11), may be present in the bone marrow (BM) for a long time without progressing to myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML); (4) the del(20)(q11) involves the minimal region of deletion typical of MDS/AML; (5) the rate of chromosome breaks is not significantly higher than in controls, from which it is concluded that SS should not be considered a breakage syndrome; (6) a specific kind of karyotype instability is present in SS, with chromosome changes possibly found in single cells or small clones, often affecting chromosomes 7 and 20, in the BM. Hence, we have confirmed our previous hypothesis that the SS mutation itself implies a mutator effect that is responsible for MDS/AML through these specific chromosome anomalies. This conclusion supports the practice of including cytogenetic monitoring in the follow-up of SS patients.
authors.affiliation: Biologia e Genetica, Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Universitá dell'lnsubria, Varese, Italy. emanuela.maserati@uninsubria.it
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maserati
authors.forename: Antonella
authors.initials: A
authors.lastname: Minelli
authors.forename: Barbara
authors.initials: B
authors.lastname: Pressato
authors.forename: Roberto
authors.initials: R
authors.lastname: Valli
authors.forename: Barbara
authors.initials: B
authors.lastname: Crescenzi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Stefanelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Menna
authors.forename: Laura
authors.initials: L
authors.lastname: Sainati
authors.forename: Furio
authors.initials: F
authors.lastname: Poli
authors.forename: Claudio
authors.initials: C
authors.lastname: Panarello
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.forename: Francesco Lo
authors.initials: FL
authors.lastname: Curto
authors.forename: Cristina
authors.initials: C
authors.lastname: Mecucci
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasquali
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009190:Myelodysplastic Syndromes / Q000209:etiology / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D013577:Syndrome; D014178:Translocation, Genetic
chemical_list: D011506:Proteins; C470521:SBDS protein, human