Chromosomal imbalance letter3q29 interstitial microdeletion syndrome: An inherited case associated with cardiac defect and normal cognition
Section snippets
Methods of detection
a-CGH was performed utilizing the CytoChip v2.0 from BlueGnome comprised of 4200 BAC clones (BlueGnome, UK). BlueFuse v3.5 (BlueGnome, UK) was used to analyze the data. Chromosome analysis was performed on the patient's peripheral blood at the 550 band level.
Chromosomal anomaly
A deletion of six adjacent BAC clones within 3q29 (Fig. 1A) was detected. The centromeric break occurred between two partially overlapping clones: RP11-185G19 (genomic region: 197.27–197.46 Mb) and RP11-252K11 (genomic region: 197.39–197.56 Mb), while the terminal breakpoint occurred between RP11-114F20 (genomic region: 198.34–198.53 Mb) and RP11-496H1 (198.82–198.98 Mb) (Table 1). Four clones covering about 1 Mb of the distal 3q29 region were intact, indicating that this deletion is
Method of confirmation
Fluorescence in situ hybridization (FISH) was performed on peripheral blood lymphocyte cultures with a commercial probe for the subtelomeric region of 3q (GS-56H22) (Abott Molecular/Vysis, USA) and BAC clones RP11-480A16, RP11-252K11, RP11-535N19, RP11-594G13 and RP11-496H1 (BacPac, USA) mapped to 3q29. Information regarding BAC clones position and band designation was obtained from NCBI database and Ensembl Genome Browser.
GS-56H22, RP11-252K11 and RP11–535N19 all showed only one copy of signal
Clinical description
The patient was born at 38 6/7 weeks to a 26 years old gravida 1, para 1 mother. Oligohydramnios was diagnosed at 36 weeks gestation. The mother developed high blood pressure at the end of pregnancy that resolved spontaneously. The patient stayed in the NICU for 57 days due to complications of meconium aspiration, primary pulmonary hypertension, PDA, subvalvular aortic stenosis and GE reflux.
At birth, the patient's weight was 3951 g (70th % ile), length was 48 cm (50th % ile) and head
Discussion
Since it was first reported in a single individual [11], 3q29 microdeletion syndrome was characterized in detail by FISH in six patients described by Willatt et al. [15]. The deletion of 1.5–1.6 Mb with almost identical molecular boundaries was shared in all six patients. However, the clinical presentations were variable, with only mild to moderate mental retardation and slight facial dysmorphism in common. The deleted segment of 3q29 was flanked by specific low copy repeats presumably
Web resources
http://www.ensembl.org (Ensembl release 50-July 2008).
http://www.ncbi.nlm.nih.gov/genome/cyto/hbrc.shtml
http://www.genome.ucsc.edu (assembly of Mar 2006).
http://projects.tcag.ca/variation (Build 36 Mar 2006).
Acknowledgments
The authors wish to acknowledge the technical expertise of the staff of the Cytogenetics Laboratory at the Kennedy Krieger Institute: Janet Biscoe, Maria Blazina, and Susan Morsey. We especially thank the patient's family for their cooperation.
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2021, Genetics in MedicineCitation Excerpt :The high frequency of dental problems among individuals with 3q29 deletion highlights the need for early and ongoing dental care. Previous literature reported elevated rates of heart defects in individuals with 3q29 deletion.2,3,21 Our findings confirm this increased risk.
3q29 microduplication syndrome: Clinical and molecular description of eleven new cases
2020, European Journal of Medical GeneticsCitation Excerpt :These duplications typically span a 1.5–1.6 Mb region that is flanked by low copies repeats (LCRs) with high identity sequences, which are known to cause increased genomic instability leading to copy number variations. The reciprocal microdeletion has also been described (MIM: 609425), and is associated with an overlapping but more severe clinical presentation (Ballif et al., 2008; Quintela et al., 2015; Willatt et al., 2005; Digilio et al., 2009; Li et al., 2009; Mulle et al., 2010; Quintero-Rivera et al., 2010). Large case-control studies identified 3q29 duplications in 6/29,085 cases and 2/19,584 controls (p = .31), which failed to demonstrate statistically significant enrichment of the duplication in individuals with neurodevelopmental phenotypes (Coe et al., 2014; Cooper et al., 2011).
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2012, Progress in Neurobiology1.3 Mb de novo deletion in chromosome band 3q29 associated with normal intelligence in a child
2010, European Journal of Medical GeneticsCitation Excerpt :Pes planus was noted bilaterally as well as laterally deviated second toes (Fig. 1) which was reported to be a familial trait. Literature review on a total of 22 cases identified with similar chromosome 3q29 microdeletions as our patient’s deletion reveals variable phenotypes associated with the 3q29 microdeletion syndrome (Table 1) [3–5]. Mild to moderate mental retardation was identified in all previously identified individuals with the possible exception of one infant/father pair [4].
Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?
2010, European Journal of Medical GeneticsCitation Excerpt :To explain how a particular CNV, such as the dup Xp22.31, can occur in both affected and healthy populations albeit with different prevalence, it was proposed that some individuals can overcome an initial impairment. This was observed for example in the microdeletion 3q29 and microduplication 7q11.23 syndromes, in which some individuals can become normal functioning adults after initially presenting mild developmental delay in infancy [1,24]. Another factor is the observation that in several genomic abnormalities, such as 3q29, 7q11.23 and 22q11.2, duplications seem to have lower penetrance than the counterpart deletions.