Fluorescence in situ hybridization detectable mosaicism for Angelman syndrome with biparental methylation

Am J Med Genet. 2000 Nov 13;95(2):145-9. doi: 10.1002/1096-8628(20001113)95:2<145::aid-ajmg10>3.0.co;2-r.


We present a child with mild to moderate global developmental delay including severe speech impairment, inappropriate happy demeanor, wide-based gait, frequent ear infections with mild hearing loss, deep-set eyes, a wide mouth, widely-spaced teeth, normal head circumference, and no seizures. Results of peripheral blood lymphocyte chromosomal analysis with GTG banding were normal. However, fluorescence in situ hybridization (FISH) studies showed mosaicism for a deletion of probes (D15S10 and SNRPN) from the Angelman syndrome (AS) critical region with approximately 40% of peripheral lymphocytes having the deletion. The deleted chromosome 15 also showed centromeric duplication, which was detected with a D15Z1 probe [46,XX, dic(15)(pter-->q11.1::p11.2-->q11. 1::q13-->qter)]. The same duplication pattern was observed in 30% of the nuclei obtained from a buccal smear. Methylation studies using polymerase chain reaction with sodium bisulfite-treated DNA demonstrated a normal biparental methylation pattern. To the best of our knowledge, this is the first case with AS and a FISH detectable deletion in a mosaic pattern. We recommend FISH studies for the detection of mosaicism in the patients with AS clinical findings even if results of the methylation studies are normal.

Publication types

  • Case Reports

MeSH terms

  • Angelman Syndrome / diagnosis*
  • Angelman Syndrome / genetics*
  • Cell Nucleus / genetics
  • Centromere / ultrastructure
  • Child, Preschool
  • Chromosome Banding
  • Chromosome Deletion
  • Chromosomes, Human, Pair 15
  • DNA Methylation*
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Female
  • Gene Deletion
  • Humans
  • In Situ Hybridization, Fluorescence / methods*
  • Male
  • Mosaicism
  • Parents
  • Prader-Willi Syndrome / genetics
  • Reproducibility of Results