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

Abstract

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.

• Authors: M Tekin, C Jackson-Cook, A Buller, A Ferreira-Gonzalez, A Pandya, C T Garrett, J Bodurtha
• Journal: American journal of medical genetics (Am J Med Genet) Vol. 95 Issue 2 Pg. 145-9 (Nov 13 2000) ISSN: 0148-7299 [Print] United States
• PMID: 11078565 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Topics

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