Interpretation of clinical relevance of X-chromosome copy number variations identified in a large cohort of individuals with cognitive disorders and/or congenital anomalies.
Genome-wide array studies are now routinely being used in the evaluation of patients with cognitive disorders (CD) and/or congenital anomalies (CA). Therefore, inevitably each clinician is confronted with the challenging task of the interpretation of copy number variations detected by genome-wide array platforms in a diagnostic setting. Clinical interpretation of autosomal copy number variations is already challenging, but assessment of the clinical relevance of copy number variations of the X-chromosome is even more complex. This study provides an overview of the X-Chromosome copy number variations that we have identified by genome-wide array analysis in a large cohort of 4407 male and female patients. We have made an interpretation of the clinical relevance of each of these copy number variations based on well-defined criteria and previous reports in literature and databases. The prevalence of X-chromosome copy number variations in this cohort was 57/4407 (∼1.3%), of which 15 (0.3%) were interpreted as (likely) pathogenic.
849 Department of Human Genetics, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. m.willemsen@gen.umcn.nl
Marjolein H
MH
Willemsen
Nicole
N
de Leeuw
Arjan P M
AP
de Brouwer
Rolph
R
Pfundt
Jayne Y
JY
Hehir-Kwa
Helger G
HG
Yntema
Willy M
WM
Nillesen
Bert B A
BB
de Vries
Hans
H
van Bokhoven
Tjitske
T
Kleefstra
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D000013:Congenital Abnormalities / Q000175:diagnosis / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D015894:Genome, Human; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis