Molecular basis of Diamond-Blackfan anemia: New findings from the Italian registry and a review of the literature

Maria Francesca Campagnoli, Emanuela Garelli, Paola Quarello, Adriana Carando, Stefania Varotto, Bruno Nobili, Daniela Longoni, Vanna Pecile, Marco Zecca, Carlo Dufour, Ugo Ramenghi, Irma Dianzani

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Background. Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40% of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25% of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress. Methods and Information Sources. We present clinical and molecular data from 97 Italian DBA patients and a review of the literature. Results and State of the Art. We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases. Perspectives. Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.

Original languageEnglish
Pages (from-to)480-489
Number of pages10
JournalHaematologica
Volume89
Issue number4
Publication statusPublished - Apr 2004

Fingerprint

Diamond-Blackfan Anemia
Registries
Mutation
Genes
Pure Red-Cell Aplasia
Genetic Translocation
Initiator Codon
Erythropoiesis
Genetic Association Studies
Stem Cell Transplantation
Missense Mutation
Rare Diseases
Point Mutation
Intellectual Disability
Dissection
Chromosomes
Erythrocytes
Alleles
Steroids

Keywords

  • Diamond-Blackfan anemia
  • Erythropoiesis
  • Mutation
  • RPS19

ASJC Scopus subject areas

  • Hematology

Cite this

Campagnoli, M. F., Garelli, E., Quarello, P., Carando, A., Varotto, S., Nobili, B., ... Dianzani, I. (2004). Molecular basis of Diamond-Blackfan anemia: New findings from the Italian registry and a review of the literature. Haematologica, 89(4), 480-489.

Molecular basis of Diamond-Blackfan anemia : New findings from the Italian registry and a review of the literature. / Campagnoli, Maria Francesca; Garelli, Emanuela; Quarello, Paola; Carando, Adriana; Varotto, Stefania; Nobili, Bruno; Longoni, Daniela; Pecile, Vanna; Zecca, Marco; Dufour, Carlo; Ramenghi, Ugo; Dianzani, Irma.

In: Haematologica, Vol. 89, No. 4, 04.2004, p. 480-489.

Research output: Contribution to journalArticle

Campagnoli, MF, Garelli, E, Quarello, P, Carando, A, Varotto, S, Nobili, B, Longoni, D, Pecile, V, Zecca, M, Dufour, C, Ramenghi, U & Dianzani, I 2004, 'Molecular basis of Diamond-Blackfan anemia: New findings from the Italian registry and a review of the literature', Haematologica, vol. 89, no. 4, pp. 480-489.
Campagnoli MF, Garelli E, Quarello P, Carando A, Varotto S, Nobili B et al. Molecular basis of Diamond-Blackfan anemia: New findings from the Italian registry and a review of the literature. Haematologica. 2004 Apr;89(4):480-489.
Campagnoli, Maria Francesca ; Garelli, Emanuela ; Quarello, Paola ; Carando, Adriana ; Varotto, Stefania ; Nobili, Bruno ; Longoni, Daniela ; Pecile, Vanna ; Zecca, Marco ; Dufour, Carlo ; Ramenghi, Ugo ; Dianzani, Irma. / Molecular basis of Diamond-Blackfan anemia : New findings from the Italian registry and a review of the literature. In: Haematologica. 2004 ; Vol. 89, No. 4. pp. 480-489.
@article{8dca3d7b11c94e4ab9616ea81ec148ec,
title = "Molecular basis of Diamond-Blackfan anemia: New findings from the Italian registry and a review of the literature",
abstract = "Background. Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40{\%} of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25{\%} of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress. Methods and Information Sources. We present clinical and molecular data from 97 Italian DBA patients and a review of the literature. Results and State of the Art. We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases. Perspectives. Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.",
keywords = "Diamond-Blackfan anemia, Erythropoiesis, Mutation, RPS19",
author = "Campagnoli, {Maria Francesca} and Emanuela Garelli and Paola Quarello and Adriana Carando and Stefania Varotto and Bruno Nobili and Daniela Longoni and Vanna Pecile and Marco Zecca and Carlo Dufour and Ugo Ramenghi and Irma Dianzani",
year = "2004",
month = "4",
language = "English",
volume = "89",
pages = "480--489",
journal = "Haematologica",
issn = "0390-6078",
publisher = "NLM (Medline)",
number = "4",

}

TY - JOUR

T1 - Molecular basis of Diamond-Blackfan anemia

T2 - New findings from the Italian registry and a review of the literature

AU - Campagnoli, Maria Francesca

AU - Garelli, Emanuela

AU - Quarello, Paola

AU - Carando, Adriana

AU - Varotto, Stefania

AU - Nobili, Bruno

AU - Longoni, Daniela

AU - Pecile, Vanna

AU - Zecca, Marco

AU - Dufour, Carlo

AU - Ramenghi, Ugo

AU - Dianzani, Irma

PY - 2004/4

Y1 - 2004/4

N2 - Background. Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40% of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25% of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress. Methods and Information Sources. We present clinical and molecular data from 97 Italian DBA patients and a review of the literature. Results and State of the Art. We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases. Perspectives. Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.

AB - Background. Diamond-Blackfan anemia (DBA) is a rare, pure red blood cell aplasia of childhood caused by an intrinsic defect in erythropoietic progenitors. Malformations occur in about 40% of patients. More than half of patients respond to steroids; non-responders need chronic transfusions or stem cell transplantation (SCT). Mutations in the gene encoding ribosomal protein S19 are found in 25% of patients, but the link with erythropoiesis is unclear. A second DBA locus has been found on chromosome 8p22-p23; analysis of genes of the region is in progress. Methods and Information Sources. We present clinical and molecular data from 97 Italian DBA patients and a review of the literature. Results and State of the Art. We describe five new RPS19 gene mutations: four point mutations and one unbalanced chromosomal translocation. Hematologic findings, malformations and outcome are similar in the RPS19 mutated and the non-mutated groups. No genotype-phenotype correlation has been found so far in RPS19 mutated patients. Our data, however, and a thorough review of literature show a worse outcome (expressed as transfusion dependence) in patients with mutations that completely abolish one allele, i.e. gross chromosomal rearrangements and mutations at the initiation codon. The association of mental retardation with large deletions at the 19q locus points to a contiguous gene syndrome. A recurrent missense mutation (Arg62Trp) is associated with transfusion dependence in eight of the nine reported cases. Perspectives. Nationwide collaboration and population-based registries recording molecular data are essential for the further dissection of this rare heterogeneous disease and the definition of new therapeutic trials.

KW - Diamond-Blackfan anemia

KW - Erythropoiesis

KW - Mutation

KW - RPS19

UR - http://www.scopus.com/inward/record.url?scp=2942724097&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942724097&partnerID=8YFLogxK

M3 - Article

C2 - 15075082

AN - SCOPUS:2942724097

VL - 89

SP - 480

EP - 489

JO - Haematologica

JF - Haematologica

SN - 0390-6078

IS - 4

ER -