TY - JOUR
T1 - Copy number variants on the X chromosome in women with primary ovarian insufficiency
AU - Knauff, Erik A. H.
AU - Blauw, Hylke M.
AU - Pearson, Peter L.
AU - Kok, Klaas
AU - Wijmenga, Cisca
AU - Veldink, Jan H.
AU - van den Berg, Leonard H.
AU - Bouchard, Philippe
AU - Fauser, Bart C. J. M.
AU - Dutch Primary Ovarian Insufficiency Consortium
AU - Evers, Johannes
AU - Franke, Lude
PY - 2011/4
Y1 - 2011/4
N2 - To investigate whether submicroscopic copy number variants (CNVs) on the X chromosome can be identified in women with primary ovarian insufficiency (POI), defined as spontaneous secondary amenorrhea before 40 years of age accompanied by follicle-stimulating hormone levels above 40 IU/L on at least two occasions.Analysis of intensity data of single nucleotide polymorphism (SNP) probes generated by genomewide Illumina 370k CNV BeadChips, followed by the validation of identified loci using a custom designed ultra-high-density comparative genomic hybridization array containing 48,325 probes evenly distributed over the X chromosome.Multicenter genetic cohort study in the Netherlands.108 Dutch Caucasian women with POI, 97 of whom passed quality control, who had a normal karyogram and absent fragile X premutation, and 235 healthy Dutch Caucasian women as controls.None.Amount and locus of X chromosomal microdeletions or duplications.Intensity differences between SNP probes identify microdeletions and duplications. The initial analysis identified an overrepresentation of deletions in POI patients. Moreover, CNVs in two genes on the Xq21.3 locus (i.e., PCDH11X and TGIF2LX) were statistically significantly associated with the POI phenotype. Mean size of identified CNVs was 262 kb. However, in the validation study the identified putative Xq21.3 deletions samples did not show deviations in intensities in consecutive probes.X chromosomal submicroscopic CNVs do not play a major role in Caucasian POI patients. We provide guidelines on how submicroscopic cytogenetic POI research should be conducted. American Society for Reproductive Medicine.
AB - To investigate whether submicroscopic copy number variants (CNVs) on the X chromosome can be identified in women with primary ovarian insufficiency (POI), defined as spontaneous secondary amenorrhea before 40 years of age accompanied by follicle-stimulating hormone levels above 40 IU/L on at least two occasions.Analysis of intensity data of single nucleotide polymorphism (SNP) probes generated by genomewide Illumina 370k CNV BeadChips, followed by the validation of identified loci using a custom designed ultra-high-density comparative genomic hybridization array containing 48,325 probes evenly distributed over the X chromosome.Multicenter genetic cohort study in the Netherlands.108 Dutch Caucasian women with POI, 97 of whom passed quality control, who had a normal karyogram and absent fragile X premutation, and 235 healthy Dutch Caucasian women as controls.None.Amount and locus of X chromosomal microdeletions or duplications.Intensity differences between SNP probes identify microdeletions and duplications. The initial analysis identified an overrepresentation of deletions in POI patients. Moreover, CNVs in two genes on the Xq21.3 locus (i.e., PCDH11X and TGIF2LX) were statistically significantly associated with the POI phenotype. Mean size of identified CNVs was 262 kb. However, in the validation study the identified putative Xq21.3 deletions samples did not show deviations in intensities in consecutive probes.X chromosomal submicroscopic CNVs do not play a major role in Caucasian POI patients. We provide guidelines on how submicroscopic cytogenetic POI research should be conducted. American Society for Reproductive Medicine.
KW - Copy number variation
KW - premature ovarian failure
KW - primary ovarian insufficiency
KW - X chromosome
U2 - 10.1016/j.fertnstert.2011.01.018
DO - 10.1016/j.fertnstert.2011.01.018
M3 - Article
C2 - 21316664
SN - 0015-0282
VL - 95
SP - 1584-U74
JO - Fertility and Sterility
JF - Fertility and Sterility
IS - 5
ER -