Abstract for presentation at 11th International Congress of Human Genetics

A novel 3.5 Mb interstitial deletion of chromosome 15q24.1-q24.3 detected by array CGH and review of the literature

  • Eva Klopocki, Institute of Medical Genetics, Charité Universitätsmedizin Berlin, Germany
  • Ulrike Grieben, Deparment of Neuropediatrics, Charité Universitätsmedizin Berlin, Germany
  • Luitgard Neumann, Institute of Human Genetics, Charité Universitätsmedizin Berlin, Germany
  • Denise Horn, Institute of Medical Genetics, Charité Universitätsmedizin Berlin, Germany
  • Holger Tönnies, Institute of Human Genetics, Charité Universitätsmedizin Berlin, Germany
  • Hans-Hilger Ropers, Max-Planck Institute for Molecular Genetics, Berlin, Germany
  • Stefan Mundlos, Institute of Medical Genetics, Charité Universitätsmedizin Berlin, Germany
  • Reinhard Ullmann, Max-Planck Institute for Molecular Genetics, Berlin, Germany

    • Background: We report on a ten year old boy with developmental retardation, craniofacial dysmorphisms, truncal obesity and genital abnormalities (micropenis). In addition muscular hypotonia, strabism and splenomegaly were observed; inguinal and umbilical hernias were surgically corrected. A metabolic defect was suspected.
    Methods: Chromosome analysis and FISH (SNRPN and TUPLE 1) as well as metabolic screening were performed. We used a whole genome tiling path array consisting of more than 36,000 BAC clones to investigate the patient’s genomic DNA for submicroscopic aberrations.
    Results: Mucopolysaccharidoses and CDG syndrome were ruled out. Chromosome analysis revealed a normal male karyotype (46,XY). Prader-Willi syndrome and microdeletion 22q11.2 were excluded by FISH. A more detailed investigation of the patient’s genomic DNA by microarray-based comparative genomic hybridization (array CGH) detected an interstitial 3.5 Mb deletion within chromosomal band 15q24. The breakpoints are located within chromosomal bands 15q24.1 and 15q24.3 (arr cgh 15q24.1q24.3(RP11-775D01→RP11-91J09)x1). FISH analysis using three BAC clones confirmed the microdeletion on chromosome 15q24. Investigation of the parents gave normal results. The deletion encompasses ~30 genes. Among the deleted genes are genes coding for metabolic enzymes, e.g. mannose phosphate isomerase (MPI), alpha-mannosidase 2C1 (MAN2C1), and alpha-subunit of electron transfer flavoprotein (ETFA), as well as the steroidogenic enzyme P450scc which catalyzes the first step in steroidogenesis.
    Conclusions: Interstitial deletions involving 15q24 have been described in only nine patients to date. The clinical phenotype of these cases is similar to our patient and includes developmental delay, muscular hypotonia, and genital abnormalities in males. This is the smallest interstitial deletion at chromosome 15q24 reported so far. We present a genotype – phenotype correlation and comparison to the nine cases from the literature.

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