BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1 - PubMed (original) (raw)

BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1

Anna Brunet et al. BMC Med Genet. 2009.

Abstract

Background: Microdeletion of the chromosome 22q11.2 region is the most common genetic aberration among patients with velocardiofacial syndrome (VCFS) but a subset of subjects do not show alterations of this chromosome region.

Methods: We analyzed 18 patients with VCFS-like features by comparative genomic hybridisation (aCGH) array and performed a face-to-face slide hybridization with two different arrays: a whole genome and a chromosome 22-specific BAC array. Putative rearrangements were confirmed by FISH and MLPA assays.

Results: One patient carried a combination of rearrangements on 1q21.1, consisting in a microduplication of 212 kb and a close microdeletion of 1.15 Mb, previously reported in patients with variable phenotypes, including mental retardation, congenital heart defects (CHD) and schizophrenia. While 326 control samples were negative for both 1q21.1 rearrangements, one of 73 patients carried the same 212-kb microduplication, reciprocal to TAR microdeletion syndrome. Also, we detected four copy number variants (CNVs) inherited from one parent (a 744-kb duplication on 10q11.22; a 160 kb duplication and deletion on 22q11.21 in two cases; and a gain of 140 kb on 22q13.2), not present in control subjects, raising the potential role of these CNVs in the VCFS-like phenotype.

Conclusions: Our results confirmed aCGH as a successful strategy in order to characterize additional submicroscopic aberrations in patients with VCF-like features that fail to show alterations in 22q11.2 region. We report a 212-kb microduplication on 1q21.1, detected in two patients, which may contribute to CHD.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Genomic imbalances on chromosome 1q21.1. A: 5.6K whole genome BAC aCGH profiles for patient V5 on chromosome region 1q21.1. Each dot represents the mean log2 ratio transformed after Lowess normalization (y-axis) from four independent replicate spots on the array. The clones on the 1q21.1 region are displayed in the x-axis. Direct experiments (D) are shown in blue, while dye swap (DS) experiments are displayed in red. Each dot represents a BAC clone present in the aCGH experiment. B: Genome browser representation of the 1q21.1 region containing the microduplication/microdeletion. The figure shows the related segmental duplications that probably mediated the rearrangements and the genes affected. The microduplication of 212 kb (reciprocal to the TAR syndrome micodeletion), and the downstream microdeletion of 1.15 Mb are indicated by two orange bars (GAIN and LOSS).

Figure 2

Figure 2

Detection and validation of the chromosome 1q21.1 rearrangements in patient V5. A: Electropherograms showing MLPA peak patterns corresponding to familial analysis of case V5. B: Interphase and metaphase FISH images with 1q21.1 red BAC probes confirm the microduplication (RP11-293J20) and microdeletion (RP11-314N2). A Green probe generated from CTD-2180H16 BAC clone was used as a control probe from same chromosome (1p34.2).

Figure 3

Figure 3

Facial appearance and hands of patients with 1q21.1 rearangements. A: Patient V5 with microduplication/microdeletion 1q21.1: note frontal balding, arched eyebrows, deep-set eyes and thin upper lip, fingers with camptodactyly and mild interdigital membranes. B: Patient 112 with microduplication 1q21.1: Note moderate clinodactyly.

Similar articles

Cited by

References

    1. McDermid HE, Morrow BE. Genomic disorders on 22q11. Am J Hum Genet. 2002;70(5):1077–1088. doi: 10.1086/340363. - DOI - PMC - PubMed
    1. Botto LD, May K, Fernhoff PM, Correa A, Coleman K, Rasmussen SA, Merritt RK, O'Leary LA, Wong LY, Elixson EM. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics. 2003;112(1 Pt 1):101–107. doi: 10.1542/peds.112.1.101. - DOI - PubMed
    1. Ryan AK, Goodship JA, Wilson DI, Philip N, Levy A, Seidel H, Schuffenhauer S, Oechsler H, Belohradsky B, Prieur M. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997;34(10):798–804. doi: 10.1136/jmg.34.10.798. - DOI - PMC - PubMed
    1. Cohen E, Chow EW, Weksberg R, Bassett AS. Phenotype of adults with the 22q11 deletion syndrome: A review. Am J Med Genet. 1999;86(4):359–365. doi: 10.1002/(SICI)1096-8628(19991008)86:4<359::AID-AJMG10>3.0.CO;2-V. - DOI - PMC - PubMed
    1. Gerdes M, Solot C, Wang PP, Moss E, LaRossa D, Randall P, Goldmuntz E, Clark BJ, Driscoll DA, Jawad A. Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion. Am J Med Genet. 1999;85(2):127–133. doi: 10.1002/(SICI)1096-8628(19990716)85:2<127::AID-AJMG6>3.0.CO;2-F. - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources