Single-nucleotide polymorphism array genotyping is equivalent to metaphase cytogenetics for diagnosis of Turner syndrome
Siddharth Prakash, Dongchuan Guo, Cheryl L Maslen, Michael Silberbach, Dianna Milewicz, Carolyn A Bondy, GenTAC Investigators, Kathryn W Holmes, Harry C Dietz, Williams Ravekes, Kira Lurman, Dianna M Milewicz, Meghan Terry, Alana Cecchi, Scott A LeMaire, Irina Volguina, Cheryl L Maslen, Howard K Song, Victor Menashe, Jessica D Kushner, Reed E Pyeritz, Joseph E Bavaria, Megan Morales, T Basson, Richard Devereux, Jonathan W Weinsaft, Deborah McDermott, Kim Eagle, H Eser Tolunay, Patrice Desvigne-Nickens, Mario P Stylianou, Megan Mitchell, Barbara L Kroner, Donald Brambilla, Tabitha Hendershot, Danny Ringer, Meg Cunningham, Mark Kindem, Siddharth Prakash, Dongchuan Guo, Cheryl L Maslen, Michael Silberbach, Dianna Milewicz, Carolyn A Bondy, GenTAC Investigators, Kathryn W Holmes, Harry C Dietz, Williams Ravekes, Kira Lurman, Dianna M Milewicz, Meghan Terry, Alana Cecchi, Scott A LeMaire, Irina Volguina, Cheryl L Maslen, Howard K Song, Victor Menashe, Jessica D Kushner, Reed E Pyeritz, Joseph E Bavaria, Megan Morales, T Basson, Richard Devereux, Jonathan W Weinsaft, Deborah McDermott, Kim Eagle, H Eser Tolunay, Patrice Desvigne-Nickens, Mario P Stylianou, Megan Mitchell, Barbara L Kroner, Donald Brambilla, Tabitha Hendershot, Danny Ringer, Meg Cunningham, Mark Kindem
Abstract
Purpose: Turner syndrome is a developmental disorder caused by partial or complete monosomy for the X chromosome in 1 in 2,500 females. We hypothesized that single-nucleotide polymorphism (SNP) array genotyping could provide superior resolution in comparison to metaphase karyotype analysis to facilitate genotype-phenotype correlations.
Methods: We genotyped 187 Turner syndrome patients with 733,000 SNP marker arrays. All cases met diagnostic criteria for Turner syndrome based on karyotypes (60%) or characteristic physical features. The SNP array results confirmed the diagnosis of Turner syndrome in 100% of cases.
Results: We identified a single X chromosome (45,X) in 113 cases. In 58 additional cases (31%), other mosaic cell lines were present, including isochromosomes (16%), rings (5%), and Xp deletions (8%). The remaining cases were mosaic for monosomy X and normal male or female cell lines. Array-based models of X chromosome structure were compatible with karyotypes in 104 of 116 comparable cases (90%). We found that the SNP array data did not detect X-autosome translocations (three cases) but did identify two derivative Y chromosomes and 13 large copy-number variants that were not detected by karyotyping.
Conclusion: Our study is the first systematic comparison between the two methods and supports the utility of SNP array genotyping to address clinical and research questions in Turner syndrome.
Conflict of interest statement
CONFLICTS OF INTEREST
S.P. Nothing to disclose
D.G. Nothing to disclose
D.M.M. Nothing to disclose
C.L.M Nothing to disclose
M.S Nothing to disclose
C.A.B Nothing to disclose
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Source: PubMed