P703: A balanced insertional translocation t(2;11)(q31;p13p14) found to underlie a familial case of WAGR syndrome

Treatment and Management: Following this diagnosis, the patient underwent recommended screening including ultrasounds of the kidney and heart, which were all normal.The patient has begun estrogen replacement therapy to treat the delays in puberty and sex development.Outcome and Follow-Up: The patient will continue to be monitored for liver, heart, kidney and thyroid function as well changes to hearing, vision and endocrine levels.The patient's first-degree relatives have been offered chromosomal studies to determine if they are also rearrangement heterozygotes.Discussion: Partial trisomy 11q is a very rare cytogenetic anomaly that is often associated with the monosomy of another chromosome due to unbalanced structural rearrangement.Commonly reported features of trisomy 11q include growth retardation, craniofacial dysmorphism, intellectual disability, hypotonia, developmental delays, and birth defects.Unbalanced translocations involving the X chromosome and an autosome have an added layer of complexity when considering X-inactivation.If the X-inactivation center (XIC) is retained in the translocation, the derivative X may be preferentially inactivated, mitigating some of the adverse phenotypes related to trisomy of the autosomal segment.If the XIC is deleted, all present genes on the derivative X chromosome will be expressed. Conclusion:The cytogenetic results reported here correlate with the mild Turner Syndrome phenotypic presentation seen in this individual.Given that most of the genes on the X chromosome that escape X-inactivation are located on the p-arm retained in the major cell line and that the partial trisomy 11q is predicted to be inactivated, it is conceivable that the patient would display a milder phenotype than canonical Turner syndrome or other reported cases of 11q trisomy.Introduction: Turner syndrome occurs in approximately 1 in 2,500 live births and its typical presentation can include short stature, congenital heart defects, premature ovarian failure, skeletal anomalies, kidney issues, autoimmune disorders, infertility, mild developmental delays, behavioral issues, and other features.Although 15-25% of Turner Syndrome cases are 45,X mosaic, other mosaic turner syndrome variants involving a derivative X chromosome are incredibly rare.Case Presentation: An 18-year-old female presenting with primary ovarian failure and primary amenorrhea was referred to the Colorado Genetics Laboratory for chromosomal analysis for possible Turner Syndrome diagnosis.Diagnostic Workup: Chromosomal analysis revealed a rare mosaic Turner Syndrome result.The first cell line accounting for ~90% of analyzed cells included one normal copy of chromosome X and one unbalanced derivative X chromosome (46,X,der(X)t(X;?11)(q13.?2;q22.3)).This derivative X displayed a loss of most of the long (q) arm (approximately from Xq13.2 to the terminus) with a gain of a portion of the long (q) arm of chromosome 11 (from band q22.3 to the terminus) translocated onto Xq.A second cell line with monosomy X (45,X) was present in ~10% of cells analyzed.As the the Xq13.2 breakpoint determined by chromosome analysis in the present case may include the X-inactivation center (XIC), chromosomal microarray analysis (CMA) was performed to determine the genomic breakpoints and genes involved in the derivative chromosome.CMA confirmed the mosaic results seen by chromosome analysis, with the major cell line (>90%) containing the derivative X chromosome.The breakpoint was determined to be Xq21.1 (arr[GRCh37] Xp22.33q21.1(1_81983107)x1~2,Xq21.1q28(81988862_155270560)x1~2,11q23.1q25(112281913_135006516)x3) on the derivative chromosome, indicating the retention of the XIC and predicted inactivation of the derivative X chromosome.