A case of mosaic supernumerary ring chromosome 15 with two copies of the segment 15p11.1–q14

• Published in: American journal of medical genetics. Part A 2006-08, Vol.140A (15), p.1663-1668
• Main Authors: Zou, Ying S., McGrann, Pamela S., Uphoff, Timothy S., Van Dyke, Daniel L.
• Format: Article
• Language: English
• Subjects: Adolescent; Angelman syndrome; Angelman Syndrome - genetics; Biological and medical sciences; Blotting, Southern; Chromosomes - ultrastructure; Chromosomes, Human, Pair 15; Complex syndromes; DNA Methylation; DNA, Satellite - metabolism; Female; Humans; In Situ Hybridization, Fluorescence; Karyotyping; Malformations of the nervous system; Medical genetics; Medical sciences; Metabolic diseases; Methylation; Mosaicism; Neurology; Obesity; Phenotype; Prader-Willi Syndrome - genetics; Prader–Willi syndrome; Ribonucleoproteins, Small Nuclear - genetics; ring chromosome 15; small nuclear ribonucleoprotein polypeptide N (SNRPN); supernumerary marker chromosomes (SMC)
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31339

Although supernumerary marker chromosomes derived from chromosome 15 (SMC(15)) are the most common marker chromosome in humans, ring SMC(15)s are rare. Here we report on a 16‐month‐old patient who has a ring SMC(15) with two copies of the segment 15p11.1–q14 region. She exhibits hypotonia, developmental delay, speech delay, microstomia, micrognathia, and other mild dysmorphic features. The ring was present in 22% of her peripheral blood lymphocyte cells. FISH study revealed that the ring was derived from chromosome 15, and had neither telomere sequence nor satellite III paracentromeric DNA. It had alpha satellite DNA, and two copies of the segment 15q11.2 to CTD 2125J1 (at 15q14, 2.2 Mbp telomeric of the common breakpoint 5). The ring‐containing cells had four copies of 15p11.1–q14. The ring can be described as r(15)(::p11.1 → q14::q14 → p11.1::). Southern‐blot analysis of the methylation pattern in the PW/AS critical region showed biparental inheritance, and the ring was maternally derived. This patient's phenotype was comparable to ring SMC(15) patients with three copies of the Prader–Willi/Angelman syndrome (PWS/AS) critical region. © 2006 Wiley‐Liss, Inc.