X-autosomal translocation — a distraction or a cause of primary ovarian insufficiency?

Abstract

OBJECTIVE: To characterize the genetic basis of primary ovarian insufficiency (POI) in a patient with a balanced X-autosomal translocation involving one X chromosome and a deletion at Xq27.2 on the other X chromosome. X-autosomal translocations have been associated with POI, possibly due to aberrations in pairing or X inactivation during folliculogenesis. Additionally, the putative genes leading to POI are located at one of two loci on Xq: POF1 (Xq26-q28) or POF2 (Xq13.3-q22), with the minimal POF1 deletion associated with POI narrowed to a 10.5 Mb region at Xq27.2/Xq27.3-q28.DESIGN: Case report.MATERIALS AND METHODS: 23 year-old with oligomenorrhea and primary infertility. She reported menarche at age 13. After discontinuation of oral contraceptive pills at age 22, she experienced oligomenorrhea and infertility. There was no family history of POI. Her physical exam was unremarkable and showed no stigmata of Turner Syndrome. Relevant laboratory data included: day 3 FSH=61.2 mIU/mL, day 3 estradiol <20 pg/mL and normal FMR1 premutation testing.RESULTS: Standard karyotype testing (GTG band resolution 550) revealed 46,X,t(X;1)(q22.1;q42.1), indicating a balanced translocation involving chromosomes X and 1, with no apparent macroscopic loss of genetic material from the translocated chromosomes. Subsequent microarray comparative genomic hybridization (NimbleGen CGX-3 array) revealed a cryptic 382-482 kb deletion at Xq27.2 (arr Xq27.2(140,201,306-140,583,606)x1). In order to confirm the microarray findings and localize the deletion, fluorescence in situ hybridization (FISH) analysis was performed with a BAC probe (RP11-1082H4) mapping to the deleted region. The deletion was present on the X chromosome that was not involved in the translocation.CONCLUSION: Our patient exhibits a balanced X-autosomal translocation, which has been associated with POI, but appears to be an incidental finding in this patient. This case further narrows the minimal POF1 deletion associated with POI to a 382-482 kb deletion at Xq27.2. OBJECTIVE: To characterize the genetic basis of primary ovarian insufficiency (POI) in a patient with a balanced X-autosomal translocation involving one X chromosome and a deletion at Xq27.2 on the other X chromosome. X-autosomal translocations have been associated with POI, possibly due to aberrations in pairing or X inactivation during folliculogenesis. Additionally, the putative genes leading to POI are located at one of two loci on Xq: POF1 (Xq26-q28) or POF2 (Xq13.3-q22), with the minimal POF1 deletion associated with POI narrowed to a 10.5 Mb region at Xq27.2/Xq27.3-q28. DESIGN: Case report. MATERIALS AND METHODS: 23 year-old with oligomenorrhea and primary infertility. She reported menarche at age 13. After discontinuation of oral contraceptive pills at age 22, she experienced oligomenorrhea and infertility. There was no family history of POI. Her physical exam was unremarkable and showed no stigmata of Turner Syndrome. Relevant laboratory data included: day 3 FSH=61.2 mIU/mL, day 3 estradiol <20 pg/mL and normal FMR1 premutation testing. RESULTS: Standard karyotype testing (GTG band resolution 550) revealed 46,X,t(X;1)(q22.1;q42.1), indicating a balanced translocation involving chromosomes X and 1, with no apparent macroscopic loss of genetic material from the translocated chromosomes. Subsequent microarray comparative genomic hybridization (NimbleGen CGX-3 array) revealed a cryptic 382-482 kb deletion at Xq27.2 (arr Xq27.2(140,201,306-140,583,606)x1). In order to confirm the microarray findings and localize the deletion, fluorescence in situ hybridization (FISH) analysis was performed with a BAC probe (RP11-1082H4) mapping to the deleted region. The deletion was present on the X chromosome that was not involved in the translocation. CONCLUSION: Our patient exhibits a balanced X-autosomal translocation, which has been associated with POI, but appears to be an incidental finding in this patient. This case further narrows the minimal POF1 deletion associated with POI to a 382-482 kb deletion at Xq27.2.