Elsevier

European Journal of Medical Genetics

Volume 52, Issue 5, September–October 2009, Pages 349-352
European Journal of Medical Genetics

Chromosomal imbalance letter
3q29 interstitial microdeletion syndrome: An inherited case associated with cardiac defect and normal cognition

https://doi.org/10.1016/j.ejmg.2009.05.001Get rights and content

Abstract

An inherited, interstitial subtelomere deletion of approximately 1.3–1.4 Mb at 3q29 was identified in a patient and his father utilizing BAC array comparative genomic hybridization (a-CGH). The imbalance was located within the common 3q29 microdeletion syndrome region and shared the distal breakpoint with prior published cases. However, our patient was developmentally normal at 6 months of age and his father is a functional adult, who had mild developmental delay in childhood. They presented with congenital cardiac defects including patent ductus arteriosus. In addition, the patient had subvalvular aortic stenosis and his father had pulmonic stenosis. These defects were not present in most of the previously reported 3q29 microdeletion cases. This case expands the phenotypic findings associated with 3q29 microdeletion syndrome, suggesting an association with cardiac defect. It also raises the possibility of normal cognition in adulthood.

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.

References (15)

There are more references available in the full text version of this article.

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