Ring 21 chromosome and a satellited 1p in the same patient: Novel origin for an ectopic NOR

Abstract

Nucleolus organizer regions (NORs) are present on the satellite stalks located on the short arms of the acrocentric chromosomes. NORs present on non-acrocentric chromosomes (ectopic NORs) are rare and were reported in both phenotypically normal and abnormal individuals. We describe a patient, ascertained prenatally, with an ectopic NOR on 1p and a ring 21 chromosomes. Amniocentesis was performed at 27-weeks gestation on a 19-year-old woman after identification of intrauterine growth retardation (IUGR) by ultrasound. Cytogenetic analysis of amniocytes from the fetus showed a mos 46,XX,1ps,r(21) (p11.2q22.3)[44]/45,XX,1ps,-21[6] karyotype. Parental karyotypes were normal, indicating a de novo origin for these rearrangements in the fetus. Molecular cytogenetic characterization of the 1ps showed no loss of euchromatin and retention of the telomeric repeats. Characterization of the r(21) using array comparative genomic hybridization (CGH) identified that the deletion was approximately 5 Mb encompassing most of chromosome band 21q22.3. The ectopic NOR (1ps) was most likely derived from the acentric 21p fragment generated by the chromosome breakage event that lead to formation of the r(21) chromosome. This represents a novel mechanism for the origin of ectopic NORs. In addition, this study illustrates the importance of FISH analysis with telomeric and subtelomeric probes for characterization of chromosomes with ectopic NORs.

De novo subtelomeric deletion of 15q associated with satellite translocation in a child with developmental delay and severe growth retardation

“…It is thought that the DNA sequence in the short arms of acrocentric chromosomes is more likely to recombine with the sequence in the terminal 4q [Miller et al, 1995]. There are also reports identifying a satellite structure on other non-acrocentric chromosomes [Dev et al, 1979;Verma et al, 1979;Varley et al, 1981;Kucerova et al, 1983;van Tuinen et al, 1983;Schmid et al, 1984;Stetten et al, 1986;Harada et al, 1989;Arn et al, 1995;Faivre et al, 1999;Guttenbach et al, 1999;Storto et al, 1999;Lee et al, 2001;Willatt et al, 2001;Ki et al, 2003;Chen et al, 2004a,b] with one report on 15q which occurred as a mosaicism with ring chromosome 15 [Smith et al, 1991]. The majority of cases are familial and are detected during prenatal diagnosis [Chen et al, 2000[Chen et al, , 2004aLee et al, 2001].…”

“…This type of translocation has been reported either as rare familial polymorphisms having no phenotypic effect or de novo translocations with chromosomal loss causing abnormalities. There are several previous reports of satellited autosomes [Parslow et al, 1979;Verma et al, 1979;Watt et al, 1984;Harada et al, 1989;Estabrooks et al, 1992;Arn et al, 1995;Willatt et al, 2001;Ki et al, 2003;Chen et al, 2004a,b]. The most frequent satellited variant autosomes reported to date is chromosome 4 (4qs) [Estabrooks et al, 1992;Arn et al, 1995;Miller et al, 1995;Guttenbach et al, 1999].…”

Unique Genomic Structure and Distinct Mitotic Behavior of Ring Chromosome 21 in Two Unrelated Cases

“…A relatively normal phenotype from a ring chromosome 21 with minimal mitotic instability and absence of a terminal deletion or duplication has been reported [Papoulidis et al, 2010]. Ring chromosomes 21 with defined 3-5-Mb distal deletions and minimal mitotic instability were responsible for mild to moderate dysmorphic features and prenatal intrauterine growth retardation [Ki et al, 2003;Bertini et al, 2008]. Ring chromosomes 21 involving segmental duplication of critical regions could predict a Down syndrome or Down syndrome-like phenotype [Crombez et al, 2005].…”

“…abnormal phenotype, simple distal deletion in r(21), and variable mitotic instability [Ki et al, 2003;Bertini et al, 2008] III. Down syndrome-like phenotype, an extra r(21) or large duplicated r(21) with variable mitotic instability [Crombez et al, 2005] IV.…”

“…Recently, genome-wide oligonucleotide array comparative hybridization (aCGH) has been validated for clinical diagnosis and proven to be highly effective in defining the breakpoints and gene content of chromosomal imbalances [Xiang et al, 2008]. The application of genomic analysis defined a simple distal deletion of ring chromosome 21 in 3 cases [Ki et al, 2003;Bertini et al, 2008;Fiorini et al, 2009] and a complete ring chromosome 21 in a fetus [Papoulidis et al, 2010]. In this report, we present the unique cytogenetic and genomic findings from 2 unrelated cases of ring chromosome 21 and propose a cytogenomic approach for further characterization of the genomic structure and mitotic behavior of ring chromosomes 21.…”