title: Parental origin of the deletion del(20q) in Shwachman-Diamond patients and loss of the paternally derived allele of the imprinted L3MBTL1 gene.
abstract: Shwachman-Diamond syndrome (SDS) (OMIM 260400) is a rare autosomal recessive disease characterized by exocrine pancreatic insufficiency, skeletal, and hematological abnormalities and bone marrow (BM) dysfunction. Mutations in the SBDS gene cause SDS. Clonal chromosome anomalies are often present in BM, i(7)(q10) and del(20q) being the most frequent ones. We collected 6 SDS cases with del(20q): a cluster of imprinted genes, including L3MBTL1 and SGK2 is present in the deleted region. Only the paternal allele is expressed for these genes. Based on these data, we made the hypothesis that the loss of this region, in relation to parental origin of deletion, may be of relevance for the hematological phenotype. By comparing hematological data of our 6 cases with a group of 20 SDS patients without evidence of del(20q) in BM, we observed a significant difference for Hb levels (P < 0.012), and a difference slightly above the significance level for RBC counts (P < 0.053): in both cases the values were higher in patients with del(20q). We also report preliminary evidence for an increased number of BFU-E colonies in cases with paternal deletion, data on the presence of the deletion in colonies and in mature circulating lymphocytes. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Nacci
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Valli
authors.affiliation: Ospedale Bambino Gesù IRCCS, Oncoematologia e Medicina Trasfusionale, Roma, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Maria Pinto
authors.affiliation: Oncoematologia Pediatrica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Cystic Fibrosis Centre, Azienda Ospedaliera Universitaria, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cipolli
authors.affiliation: Department of Physics, University of Pavia, Italy.
authors.forename: Jacopo
authors.initials: J
authors.lastname: Morini
authors.affiliation: Oncoematologia Pediatrica, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Cesaro
authors.affiliation: Fondazione IRCCS Policlinico, Anatomic Pathology Section, San Matteo, Pavia, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Boveri
authors.affiliation: IRCCS Policlinico San Matteo, Center for the Study of Myelofibrosis, Biotechnology Research Area, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Rosti
authors.affiliation: Pediatrics Unit, Fondazione Medico e Brianza per il Bambino e la sua Mamma, Monza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Corti
authors.affiliation: Cystic Fibrosis Regional Center, Ospedale M. Bufalini, Cesena, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Ambroni
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pasquali
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Maserati
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Minelli
mesh_terms: D014408:Biomarkers, Tumor; D001855:Bone Marrow Diseases / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002869:Chromosome Aberrations; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D010188:Exocrine Pancreatic Insufficiency / Q000235:genetics*; D005500:Follow-Up Studies; D018392:Genomic Imprinting; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D008068:Lipomatosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012097:Repressor Proteins; D012189:Retrospective Studies; D017384:Sequence Deletion; D000081003:Shwachman-Diamond Syndrome; D025521:Tumor Suppressor Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases; C120887:L3MBTL1 protein, human