title: Unique genomic structure and distinct mitotic behavior of ring chromosome 21 in two unrelated cases.
abstract: A ring chromosome replacing a normal chromosome could involve variable structural rearrangements and mitotic instability. However, most previously reported cases lacked further genomic characterization. High-resolution oligonucleotide array comparative genomic hybridization with single-nucleotide polymorphism typing (aCGH+SNP) was used to study 2 unrelated cases with a ring chromosome 21. Case 1 had severe myopia, hypotonia, joint hypermobility, speech delay, and dysmorphic features. aCGH detected a 1.275-Mb duplication of 21q22.12-q22.13 and a 6.731-Mb distal deletion at 21q22.2. Case 2 showed severe growth and developmental retardations, intractable seizures, and dysmorphic features. aCGH revealed a contiguous pattern of a 3.612- Mb deletion of 21q22.12-q22.2, a 4.568-Mb duplication of 21q22.2-q22.3, and a 2.243-Mb distal deletion at 21q22.3. Mitotic instability was noted in 13, 30, and 76% of in vitro cultured metaphase cells, interphase cells, and leukocyte DNA, respectively. The different phenotypes of these 2 cases are likely associated with the unique genomic structure and distinct mitotic behavior of their ring chromosome 21. These 2 cases represent a subtype of ring chromosome 21 probably involving somatic dicentric ring breakage and reunion. A cytogenomic approach is proposed for characterizing the genomic structure and mitotic instability of ring chromosome abnormalities.
authors.affiliation: Department of Genetics, Yale School of Medicine, New Haven, CT 06520-8005, USA.
authors.forename: H Z
authors.initials: HZ
authors.lastname: Zhang
authors.forename: F
authors.initials: F
authors.lastname: Xu
authors.forename: M
authors.initials: M
authors.lastname: Seashore
authors.forename: P
authors.initials: P
authors.lastname: Li
mesh_terms: D002871:Chromosome Banding; D002891:Chromosomes, Human, Pair 21; D055028:Comparative Genomic Hybridization; D005260:Female; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008938:Mitosis; D020641:Polymorphism, Single Nucleotide; D012303:Ring Chromosomes