BAC array CGH in patients with Velocardiofacial syndrome-like features reveals genomic aberrations on chromosome region 1q21.1.
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.
Brunet
Anna
A
Genes and Disease Program, CIBER en Epidemiología y Salud Pública (CIBERESP), Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. abrunetv@tauli.cat
Armengol
Lluís
L
Heine
Damià
D
Rosell
Jordi
J
García-Aragonés
Manel
M
Gabau
Elisabeth
E
Estivill
Xavier
X
Guitart
Miriam
M
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D002878:Chromosomes, Human, Pair 1; D002892:Chromosomes, Human, Pair 22; D055028:Comparative Genomic Hybridization; D004062:DiGeorge Syndrome / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D055815:Young Adult