The Phenotypic Effect of X;Autosome Balanced Chromosomal Translocations: A Case with Premature Ovarian Failure and Familial t(X;9)(q22;q34)

Abuaısha A., Kaya M., Suer İ., Çefle K., Palanduz Ş., Öztürk Ş.

7. Uluslararası Erciyes Tıp Tıbbi Genetik Kongresi, Kayseri, Turkey, 26 - 28 May 2022, pp.42-43

  • Publication Type: Conference Paper / Summary Text
  • City: Kayseri
  • Country: Turkey
  • Page Numbers: pp.42-43
  • Istanbul University Affiliated: Yes


Background: Premature ovarian failure (POF) affects around 1% of women who lose ovarian function before the age of forty. POF is caused by a variety of factors, including fragile X permutations, various numerical and structural chromosomal abnormalities, autoimmune diseases, and rare syndromes, however the etiology of POF is unclear in the majority of cases. X chromosome inactivation can lead to early menopause and various reproductive problems in women with balanced or unbalanced X;autosome translocations. Unbalanced X;autosome chromosomal translocations are rare chromosomal abnormalities with broad clinical diversity, since the X chromosome imbalance is being minimized by a favorable X chromosome inactivation pattern. In most cases, this compensatory mechanism is insufficient, and patients present syndromic clinical features. A 30-years-old female referred to our Medical Genetics Department at Istanbul Faculty of Medicine Hospital with POF. Her mother had early menopause at the age of 35 and her sister has a mild intellectual disability. The patient is not married, has no children and has no known disease. She had gotten her first menstruation at the age of 13, later at the age of 20 she had unregulated menstruation, and at the age of 22 she has got amenorrhea.

Methods: TSH, Estradiol, Prolactin, LH, FSH hormone tests were requested and chromosome analysis was performed with patient's peripheral blood lymphocytes by using the standard cytogenetic GTG banding technique. Also, FMR1 gene mutation analysis were performed for the patient. Afterward, chromosome analysis was performed for the patient's mother, father and sister.

Results: The result of patient's hormone tests were TSH: 1.5 mIU/mL, Estradiol: 15.27 pg/mL, Prolactin: 21.52 ng/mL, LH: 40.12 IU/mL and FSH 90.44 mIU/mL. Patient's karyotype is 46,X,t(X;9)(q22;q34); her mother has a similar clinical presentation with the same chromosomal defect; and her sister with mild intellectual disability who is a der(Xq) carrier. The trinucleotide CGG repeat in the 5′-untranslated region of FMR1 gene is 22/36 (Normal/Normal) for the patient.

Conclusion: Various translocations that occur in the Xq critical region are thought to cause POF. It has been suggested that as a result of translocation, X chromosome meiotic pairing may be disrupted, resulting in oocyte loss. The disruption of the structure of one of the genes required for normal ovarian function as a result of translocation is another hypothesis put forward in this regard. We believe that our study is instructive and useful since it emphasizes that some anomalies which appear to be cytogenetically balanced may be unbalanced at the molecular level, shows some issues of balanced chromosomal abnormalities in real life, and demonstrates the importance of X chromosome inactivation mechanism in X;autosome chromosomal translocations.

Keywords: Premature Ovarian Failure (POF), X;Autosome Chromosomal Translocations, X Chromosome Inactivation.