TY - JOUR
T1 - DNA copy number variations in patients with 46,XY disorders of sex development
AU - Harrison, Steven M.
AU - Granberg, Candace F.
AU - Keays, Melise
AU - Hill, Martinez
AU - Grimsby, Gwen M.
AU - Baker, Linda A.
N1 - Publisher Copyright:
© 2014 American Urological Association Education and Research, Inc.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Purpose Less than 50% of cases of 46,XY disorders of sex development are genetically defined after karyotyping and/or sequencing of known causal genes. Since copy number variations are often missed by karyotyping and sequencing, we assessed patients with unexplained 46,XY disorders of sex development using array comparative genomic hybridization for possible disease causing genomic variants.Materials and Methods DNA from unexplained cases of 46,XY disorders of sex development were tested by whole genome array comparative genomic hybridization. In cases where novel copy number variations were detected parental testing was performed to identify whether copy number variations were de novo or inherited.Results Of the 12 patients who underwent array comparative genomic hybridization testing 2 had possible copy number variations causing disorders of sex development, both maternally inherited microdeletions. One case, with a maternal history of premature ovarian failure, had a cosegregating microdeletion on 9q33.3 involving NR5A1. The other case, with a maternal family history of congenital heart disease, had a cosegregating microdeletion on 8p23.1 upstream of GATA4.Conclusions In this cohort copy number variations involving or adjacent to known causal genes led to 46,XY disorders of sex development in 2 of 12 previously unexplained cases (17%). Copy number variation testing is clinically indicated for unexplained cases of 46,XY disorders of sex development to aid in genetic counseling for family planning.
AB - Purpose Less than 50% of cases of 46,XY disorders of sex development are genetically defined after karyotyping and/or sequencing of known causal genes. Since copy number variations are often missed by karyotyping and sequencing, we assessed patients with unexplained 46,XY disorders of sex development using array comparative genomic hybridization for possible disease causing genomic variants.Materials and Methods DNA from unexplained cases of 46,XY disorders of sex development were tested by whole genome array comparative genomic hybridization. In cases where novel copy number variations were detected parental testing was performed to identify whether copy number variations were de novo or inherited.Results Of the 12 patients who underwent array comparative genomic hybridization testing 2 had possible copy number variations causing disorders of sex development, both maternally inherited microdeletions. One case, with a maternal history of premature ovarian failure, had a cosegregating microdeletion on 9q33.3 involving NR5A1. The other case, with a maternal family history of congenital heart disease, had a cosegregating microdeletion on 8p23.1 upstream of GATA4.Conclusions In this cohort copy number variations involving or adjacent to known causal genes led to 46,XY disorders of sex development in 2 of 12 previously unexplained cases (17%). Copy number variation testing is clinically indicated for unexplained cases of 46,XY disorders of sex development to aid in genetic counseling for family planning.
KW - DNA copy number variations
KW - comparative genomic hybridization
KW - disorders of sex development
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U2 - 10.1016/j.juro.2014.06.040
DO - 10.1016/j.juro.2014.06.040
M3 - Article
C2 - 24946221
AN - SCOPUS:84913583835
SN - 0022-5347
VL - 192
SP - 1801
EP - 1806
JO - Journal of Urology
JF - Journal of Urology
IS - 6
ER -