Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome

Markéta Šutajová, Ursula Neukirchen, Peter Meinecke, E. Czeizel, László Tímár, Enikö Sólyom, Andreas Gal, Kerstin Kutsche

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

We studied a female patient initially diagnosed with Costello syndrome who carries an apparently balanced translocation, t(1;22) (q24.3;q13.1). Molecular characterization of the translocation revealed a mosaic of two derivative chromosomes 1 in her peripheral blood lymphocytes, in one of which the coding region of the platelet-derived growth factor (PDGFB; chromosome 22q13.1) gene was disrupted. Both the initial translocation and the secondary intrachromosomal rearrangement appear to have occurred by nonhomologous (illegitimate) recombination. In 18 patients with Costello syndrome, mutation analysis of the genes belonging to the PDGF/R family, PDGFA, PDGFB, PDGFC, PDGFD, PDGFRA, and PDGFRB, revealed no pathogenic mutations. Reevaluation of the clinical symptoms of the translocation patient challenges the diagnosis of Costello syndrome in this patient. In total RNA isolated from lymphocytes of the translocation patient, we identified four different fusion transcripts consisting of PDGFB exons and parts of chromosome 1q24.3. In two of the mRNAs, exon 6 of PDGFB, encoding the 41 C-terminal amino acid residues, was absent. Immunofluorescence analysis showed that the wild-type protein was dispersed and formed a network-like structure in the extracellular matrix, whereas the two aberrant PDGFB proteins were localized in aggregates. We speculate that the biological consequences of the mutant PDGFB allele contributed to the unique disease phenotype of the translocation patient.

Original languageEnglish
Pages (from-to)883-892
Number of pages10
JournalGenomics
Volume83
Issue number5
DOIs
Publication statusPublished - May 2004

Fingerprint

Costello Syndrome
sis Genes
Proto-Oncogene Proteins c-sis
Exons
Chromosomes
Lymphocytes
Platelet-Derived Growth Factor beta Receptor
Mutation
Chromosomes, Human, Pair 1
Platelet-Derived Growth Factor
Genetic Recombination
Genes
Fluorescent Antibody Technique
Extracellular Matrix
Proteins
Alleles
RNA
Phenotype
Amino Acids
Messenger RNA

Keywords

  • 1q24.3
  • 22q13.1
  • Chromosomal rearrangement
  • Extracellular matrix
  • Fusion transcript
  • Illegitimate recombination
  • Mutation screening
  • PDGF/R family

ASJC Scopus subject areas

  • Genetics

Cite this

Šutajová, M., Neukirchen, U., Meinecke, P., Czeizel, E., Tímár, L., Sólyom, E., ... Kutsche, K. (2004). Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome. Genomics, 83(5), 883-892. https://doi.org/10.1016/j.ygeno.2003.10.012

Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome. / Šutajová, Markéta; Neukirchen, Ursula; Meinecke, Peter; Czeizel, E.; Tímár, László; Sólyom, Enikö; Gal, Andreas; Kutsche, Kerstin.

In: Genomics, Vol. 83, No. 5, 05.2004, p. 883-892.

Research output: Contribution to journalArticle

Šutajová, M, Neukirchen, U, Meinecke, P, Czeizel, E, Tímár, L, Sólyom, E, Gal, A & Kutsche, K 2004, 'Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome', Genomics, vol. 83, no. 5, pp. 883-892. https://doi.org/10.1016/j.ygeno.2003.10.012
Šutajová, Markéta ; Neukirchen, Ursula ; Meinecke, Peter ; Czeizel, E. ; Tímár, László ; Sólyom, Enikö ; Gal, Andreas ; Kutsche, Kerstin. / Disruption of the PDGFB gene in a 1;22 translocation patient does not cause Costello syndrome. In: Genomics. 2004 ; Vol. 83, No. 5. pp. 883-892.
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