X-chromosome tiling path array detection of copy number variants in patients with chromosome X-linked mental retardation.
BACKGROUND
Aproximately 5-10% of cases of mental retardation in males are due to copy number variations (CNV) on the X chromosome. Novel technologies, such as array comparative genomic hybridization (aCGH), may help to uncover cryptic rearrangements in X-linked mental retardation (XLMR) patients. We have constructed an X-chromosome tiling path array using bacterial artificial chromosomes (BACs) and validated it using samples with cytogenetically defined copy number changes. We have studied 54 patients with idiopathic mental retardation and 20 controls subjects.


RESULTS
Known genomic aberrations were reliably detected on the array and eight novel submicroscopic imbalances, likely causative for the mental retardation (MR) phenotype, were detected. Putatively pathogenic rearrangements included three deletions and five duplications (ranging between 82 kb to one Mb), all but two affecting genes previously known to be responsible for XLMR. Additionally, we describe different CNV regions with significant different frequencies in XLMR and control subjects (44% vs. 20%).


CONCLUSIONS
This tiling path array of the human X chromosome has proven successful for the detection and characterization of known rearrangements and novel CNVs in XLMR patients.
Biochemistry and Molecular Genetics Department, Hospital Clínic and IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain. imadriba@gmail.com
I
I
Madrigal
L
L
Rodríguez-Revenga
L
L
Armengol
E
E
González
B
B
Rodriguez
C
C
Badenas
A
A
Sánchez
F
F
Martínez
M
M
Guitart
I
I
Fernández
J A
JA
Arranz
Mi
M
Tejada
L A
LA
Pérez-Jurado
X
X
Estivill
M
M
Milà
D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D041321:Chromosomes, Human, X; D017353:Gene Deletion; D018628:Gene Dosage; D020440:Gene Duplication; D014644:Genetic Variation; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D046228:Microarray Analysis / Q000379:methods*; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012680:Sensitivity and Specificity