Interstitial microduplication of Xp22.31: Causative of intellectual disability or benign copy number variant?
The use of comparative genomic hybridization (CGH) and single nucleotide polymorphism (SNP) arrays has dramatically altered the approach to identification of genetic alterations that can explain intellectual disability and /or congenital anomalies. However, the discovery of numerous copy number changes with benign or unknown clinical significance has made interpretation problematic. Submicroscopic duplication of Xp22.31 has been reported as either a possible cause of intellectual disability and/or developmental delay or a benign variant. Here we report 29 individuals with the microduplication found as part of microarray analysis of 7793 samples submitted to an international group of 13 clinical laboratories. The referral reasons varied and included developmental delay, intellectual disability, autism, dysmorphic features and/or multiple congenital anomalies. The size of the Xp22.31 duplication varied between 149 kb and 1.74 Mb and included the steroid sulfatase (STS) gene with the male to female ratio of 0.7. Duplication within this segment is seen at a frequency of 0.15% in a healthy control population, whereas a frequency of 0.37% was observed in our cohort of individuals with abnormal phenotypes. We present a detailed comparison of the breakpoints, inheritance, X-inactivation and clinical phenotype in our cohort and a review of the literature for a total of 41 patients. To date, this report is the largest compilation of clinical and array data regarding the microduplication of Xp22.31 and will serve to broaden the knowledge of regions involving copy number variation (CNV).
Li
Feng
F
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.
Shen
Yiping
Y
Köhler
Udo
U
Sharkey
Freddie H
FH
Menon
Deepa
D
Coulleaux
Laurence
L
Malan
Valérie
V
Rio
Marlène
M
McMullan
Dominic J
DJ
Cox
H
H
Fagan
Kerry A
KA
Gaunt
Lorraine
L
Metcalfe
Kay
K
Heinrich
Uwe
U
Hislop
Gordon
G
Maye
Una
U
Sutcliffe
Maxine
M
Wu
Bai-Lin
BL
Thiel
Brian D
BD
Mulchandani
Surabhi
S
Conlin
Laura K
LK
Spinner
Nancy B
NB
Murphy
Kathleen M
KM
Batista
Denise A S
DA
D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D014644:Genetic Variation; D005824:Genetics, Behavioral; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D043266:Steryl-Sulfatase / Q000235:genetics; D049951:X Chromosome Inactivation
D043266:Steryl-Sulfatase