Fluorescence in situ hybridization detectable mosaicism for Angelman syndrome with biparental methylation.
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.
Tekin
M
M
Department of Human Genetics, Virginia Commonwealth University/Medical College of Virginia, Richmond, Virginia 23298, USA.
Jackson-Cook
C
C
Buller
A
A
Ferreira-Gonzalez
A
A
Pandya
A
A
Garrett
C T
CT
Bodurtha
J
J
D017204:Angelman Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002467:Cell Nucleus / Q000235:genetics; D002503:Centromere / Q000648:ultrastructure; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15; D019175:DNA Methylation; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D009030:Mosaicism; D010290:Parents; D011218:Prader-Willi Syndrome / Q000235:genetics; D015203:Reproducibility of Results