Mehmet KOCABEY, Elçin BORA, Murat Derya ERÇAL, Tufan ÇANKAYA

TEKRARLAYAN GEBELİK KAYIPLARI BULUNAN OLGUDA SAPTANAN 48,XY,+7,+21 VE 47,XX,+16 FETAL KARYOTİPLER

Erken gebelik kaybı, klinik gebeliklerin yaklaşık %10'unun sonucudur ve kromozomal anomaliler en az %50'sindeki temel nedendir. Bu yazıda ardışık düşüklerde farklı anöploidiler saptanan bir olgu üzerinden anöploidi mekanizmaları ve takipte düşünülmesi gereken seçenekler tartışılmıştır. Otuz beş yaşında kadın spontan abortus ile başvurdu. Kantitatif floresan PCR, trizomi 21 ile uyumluydu. Ancak kültür süreci sonunda yapılan karyotipleme 48,XY,+7,+21 çift trizomisini ortaya çıkardı. Olgunun takibinde başka bir düşük 47,XX,+16 olarak saptandı. Periferik kandan sitogenetik analizinde sınırda mozaik 46,XX[95]/45,X[5] karyotipi görüldü. Fizik muayenesi normaldi fakat abdominal ultrasonografide sol böbrekte çift üreter ve aksesuar dalak mevcuttu. Tekrarlayan trizomilerin olası nedenlerinden Robertsonian translokasyonlar, yapısal anomaliler veya trizomi mozaikliği dışlandı. Düşük oranlı 45,X mozaikliği ise oosit rezervini azalttığından riski arttırabilir. Olgudaki malformasyonlar mozaikliğin genitoüriner sistemde daha yüksek oranlı olabileceğini göstermektedir. Over biyopsisi invaziv doğası nedeniyle yapılamadığından bu oranının bilinmesi mümkün değildir. Tanı ve tedavi seçeneklerinin sınırlı kaldığı benzer vakaların yönetiminde genetik danışma hayati öneme sahiptir.

Anahtar Kelimeler:

Anöploidi, Trizomi, Tekrarlayan Düşük, Cinsiyet Kromozom Aberasyonları

48,XY,+7,+21 AND 47,XX,+16 FETAL KARYOTYPES IN A CASE WITH RECURRENT PREGNANCY LOSS

Early pregnancy loss is the outcome of approximately 10% of clinically recognized pregnancies and chromosomal abnormalities are the underlying reason in 50%. In this report we discussed aneuploidy mechanisms and management options based on a couple with recurrent aneuploidies. Thirty-five-year-old female was referred with spontaneous abortion. Quantitative Fluorescent PCR was consistent with trisomy 21 but karyotyping revealed double trisomy of 48,XY,+7,+21. During follow-up, another abortion was diagnosed as 47,XX,+16. Peripheral blood analysis revealed a borderline mosaic 46,XX[95]/45,X[5] karyotype. Her physical examination was normal but abdominal ultrasonography revealed accessory spleen and double ureter in left kidney. We excluded Robertsonian translocations, structural aberrations or trisomic mosaicism as a cause but the borderline 45,X mosaicism may be the triggering factor by decreasing oocyte reserve. Presence of urinary malformation indicates that genitourinary mosaicism may be higher, although ovarian biopsy cannot be performed to determine it. Genetic counseling is vital in management of such cases.

Keywords:

Aneuploidy, Trisomy, Habitual Abortion, Sex Chromosome Aberrations,

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Committee on Practice Bulletins—Gynecology. The American College of Obstetricians and Gynecologists Practice Bulletin no. 150. Early pregnancy loss. Obstet Gynecol. 2015;125:1258-1267.
Sherman SL, Freeman SB, Allen EG, Lamb NE. Risk factors for nondisjunction of trisomy 21. Cytogenet Genome Res. 2005;111:273-280.
Bianco K, Caughey AB, Shaffer BL, Davis R, Norton ME. History of miscarriage and increased incidence of fetal aneuploidy in subsequent pregnancy. Obstet Gynecol. 2006;107:1098-1102.
Warburton D, Dallaire L, Thangavelu M, Ross L, Levin B, Kline J. Trisomy recurrence: a reconsideration based on North American data. Am J Hum Genet. 2004;75:376-385.
Micale M, Insko J, Ebrahim SAD, Adeyinka A, Runke C, Van Dyke DL. Double trisomy revisited--a multicenter experience. Prenat Diagn. 2010;30:173-176.
Malhes JB, Moore CM, Gershank JJ. A case of double trisomy in a liveborn infant: 48, XXY, "13. Clin Genet. 1977;11:147-150.
Angell RR. Predivision in human oocytes at meiosis I: a mechanism for trisomy formation in man. Hum Genet. 1991;86:383-387.
Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2:280-291.
Gabriel AS, Thornhill AR, Ottolini CS, et al. Array comparative genomic hybridisation on first polar bodies suggests that non-disjunction is not the predominant mechanism leading to aneuploidy in humans. J Med Genet. 2011;48:433-437.
Ottolini CS, Newnham L, Capalbo A, et al. Genome-wide maps of recombination and chromosome segregation in human oocytes and embryos show selection for maternal recombination rates. Nat Genet. 2015;47:727-735.
Hassold T, Chen N, Funkhouser J, et al. A cytogenetic study of 1000 spontaneous abortions. Ann Hum Genet. 1980;44:151-178.
McCoy RC, Demko ZP, Ryan A, et al. Evidence of Selection against Complex Mitotic-Origin Aneuploidy during Preimplantation Development. Arnheim N, ed. PLOS Genet. 2015;11:e1005601.
Munné S, Sandalinas M, Magli C, Gianaroli L, Cohen J, Warburton D. Increased rate of aneuploid embryos in young women with previous aneuploid conceptions. Prenat Diagn. 2004;24:638-643.
Russell LM, Strike P, Browne CE, Jacobs PA. X chromosome loss and ageing. Cytogenet Genome Res. 2007;116:181-185.
Subramaniyam S, Pulijaal VR, Mathew S. Double and multiple chromosomal aneuploidies in spontaneous abortions: A single institutional experience. J Hum Reprod Sci. 2014;7:262-268.