title: A balanced chromosomal translocation involving chromosomes 3 and 16 in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome reveals new candidate genes at 3p22.3 and 16p13.3.
abstract: BACKGROUND
  Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome, or the congenital absence of uterus and vagina, is the most severe anomaly of the female reproductive tract. It affects 1 in 5,000 females, and is the second most common cause of primary amenorrhea. The etiology remains unknown in most patients, although four single gene defects and some repetitive copy number variants (CNVs) have been identified. Translocations in MRKH patients are very rare, and reported only in three patients previously without breakpoint mapping. We have identified the fourth MRKH translocation patient and are the first to characterize the breakpoints mapped by molecular methods.
  
  
  RESULTS
  The proband is a 17- year old white female with agenesis of the uterus and vagina who had a peripheral blood karyotype revealing a de novo balanced translocation 46,XX,t(3;16)(p22.3;p13.3)dn. There were no known related anomalies present in the proband or her family. No CNVs were found by chromosomal microarray analysis, and no genes were directly disrupted by the translocation. DNA sequencing of six nearby candidate genes-TRIM71, CNOT10, ZNF200, OR1F1, ZNF205, and ZNF213-did not reveal any mutations. RT-qPCR of proband lymphoblast RNA for 20 genes near the breakpoints of 3p22.3 and 16p13.3 showed significantly altered expression levels for four genes in the proband compared to three white female controls, after correction for multiple comparisons. Reduced expression was seen for CMTM7 and CCR4 on 3p22.3, while increased expression was observed for IL32 and MEFV on 16p13.3.
  
  
  CONCLUSIONS
  We have mapped the breakpoints of our t(3;16)(p22.3;p13.3) translocation patient using molecular methods to within 13.6 kb at 3p22.3 and within 1.9 kb for 16p13.3 and have suggested 10 nearby genes that become plausible candidate genes for future study.
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA USA.
authors.forename: Lacey S
authors.initials: LS
authors.lastname: Williams
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA USA.
authors.forename: Hyung-Goo
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Research Group Development and Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Kalscheuer
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA USA.
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Tuck
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA USA.
authors.forename: Lynn P
authors.initials: LP
authors.lastname: Chorich
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Sullivan
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Falkenstrom
authors.affiliation: American Society for Reproductive Medicine, Birmingham, AL USA.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Reindollar
authors.affiliation: Section of Reproductive Endocrinology, Infertility, & Genetics, Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta University, Augusta, GA USA ; Department of Neuroscience & Regenerative Medicine, Augusta University, Augusta, GA 30912 USA ; Department of Physiology, Medical College of Georgia, Augusta University, Augusta, GA 30912 USA.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Layman