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A rare de novo balanced X; 1 translocation in an Indian female with primary amenorrhea.


Primary amenorrhea is the complete absence of menstruation. Amenorrhea is a normal clinical feature in pre-pubertal, pregnant, and postmenopausal women. It has a strong correlation with the expression of X chromosome. It has been reported that the percentage of chromosomal abnormalities varies from 15.9% to 63.3% in patients with primary amenorrhea (1, 2). It also accounts for 20% cases of patients with infertility. X; autosome translocations are uncommon and are associated with a variable phenotype with an incidence of approximately 1:30,000 live births. Due to non-random X-inactivation, the majority of X; autosome carriers that present with abnormal phenotypes include multiple congenital abnormalities, developmental delay, a recognizable X-linked syndrome or gonadal dysgenesis (3). In this report, the clinical, biochemical and cytogenetic aspects of a healthy, non dysmorphic 24 years old female with the complaint of primary amenorrhea was presented.

Case Presentation

The proposita, 24 year-old female with the complaint of primary amenorrhea, was referred to Institute of Genetics and Hospital for Genetic Diseases, Osmania University for cytogenetic evaluation in the year 2013. She was born to a nonconsanguineous parent and her siblings were healthy. Her physical examination revealed normal height and weight of 168 cm and 73.5 kg, respectively. She showed fairly normal intelligence. Her biochemical laboratory investigations were found to be normal with a hormonal profile of 6.8 ng/ml of prolactin (normal range 3-25 ng/ml), 13.9 mIU/ml of follicle stimulating hormone (FSH ref range. 10-15 mlU/ml) and 11.2 mlU/ml of luteinizing hormone (LH ref range. 10-15 mlU/ml). Thyroid profile was also found to be normal with TSH=0.66 mlU/ml (0.4-4.2 mlU/ml) T3=1.08 ng/ ml (0.8-1.9 ng/ml) and T4=110 ng/ml (50-130 ng/ ml). Ultrasound examination of the pelvis revealed bilateral streak gonads (right ovary: 2.1x 1.9 cm and left ovary: 2.7x2.1 cm) and a markedly hypoplastic uterus measuring 4.9x2.7 cm. Normal vagina and cervix were present and there was no abnormality of the external genitalia. The female had been on low level of contraceptive pills for several years for cyclic estrogen and progesterone replacement and to induce menses, but had never menstruated spontaneously.

Cytogenetic analysis of the peripheral blood lymphocytes of the proband was carried out according to the modified method of Moorhead et al. (4). Peripheral blood lymphocytes were stimulated with phytohemagglutinin and harvested at 68th hr with colchicine. Hypotonic treatment was given to the cells and then they were fixed with Carnoy's fixative. Standard GTG banding was done according to the method of Seabright (5). Karyotype analysis of 50 metaphases revealed a pattern of 46, X, t(X;1)(q21;p32), suggestive of a balanced sex autosome translocation involving the long arm of chromosome X and short arm of chromosome 1 (Figure 1). ISCN guidelines for the chromosomal nomenclature (2013) were followed for the karyotype analysis (6). The translocation was found to be de novo as the parental karyotypes were normal.


Genes essential for normal ovarian development are located on both arms of the X chromosome (7). An abnormality in the number or the structure of the X chromosome results in the disturbance in the normal process of translation of genetic sex and final determination of the phenotypic sex (8). Thus, the abnormal phenotypes are the consequences of the gene disruption, position effect or deletion at one of the break points resulting in haploinsufficiency of critical X linked genes.

The present study revealed a rare de novo sex autosome translocation in a female with primary amenorrhea. Cytogenetic analysis revealed 46,X,t (X;1)(q21;p32) karyotype indicating its possible association with amenorrhea. As there is no published data on X and 1 translocation with these break points, this case can be considered as a novel X, autosome translocation in primary amenorrhea. However, Waters et al. published a report on X autosome translocations from UK population with 104 cases from different laboratories in UK. Among them, 5 cases were found with X; 1 translocation with different clinical manifestations (Table 1) (9).

Vidhya et al. (2009) reported X; 7 translocation in a female with hypergonadotropic amenorrhea (10). Omrani et al. (2012) reported X; 9 translocation in a female with premature ovarian failure (11). Chen et al. (2014) reported an association of primary amenorrhea and mental retardation with concomitant unbalanced X; 6 translocation and X chromosome rearrangements (12). Additional studies showed that Xq13-q26 was particularly a crucial section of chromosome X, since loss or disruption of this region results in severe impairment in ovarian function (13). Our study is in agreement with the hypothesis supported by a review of balanced X autosome translocations where 23 of 36 phenotypic females had POF (premature ovarian failure) with a break point between Xq13 and Xq26. The genes DIAPH2, XPNEP2, DACH2, POF1B, CHM and NXF5, are some of the candidates that are present on X chromosome which are interrupted by the Autosome and X translocations (14).

Our case report is believed to be the first description of a balanced X; 1 translocation with break points (Xq21 and 1p32) in a female with primary amenorrhea. As the proband manifested non dysmorphic features or developmental delay with normal hormonal profile, the impact of X; 1 translocation appears to be limited to ovarian structure and function. Since the break point was in the critical region of the X chromosome, therefore, it is probable that her chromosomal abnormality was responsible for her critical state. Thus, the reported de novo translocation in a phenotypically normal female with primary amennorhea could be due to the deleterious effects related to disruption of essential genes on X chromosome.


The X autosome translocations advance the understanding of clinical and cytogenetic basis for amenorrhea. Thus, the precise diagnosis and evaluation of patients with sex chromosome abnormality with conventional cytogenetic analysis is essential for the evaluation of phenotype and karyotype correlations, followed by genetic counseling.


Authors thank Mr. B. Kishore and Mr. M. Panduranga Chary for their technical assistance and Department of Biotechnology, New Delhi for the financial assistance.

Conflict of Interest

The authors declare no conflict of interest.


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(2.) Joseph A, Thomas IM. Cytogenetic investigations in 150 cases with complaints of sterility or primary amenorrhea. Hum Genet. 1982;61(2):105-9.

(3.) Sharp AJ, Spotswood HT, Robinson DO, Turner BM, Jacobs PA. Molecular and cytogenetic analysis of the spreading of X inactivation in X;autosome translocations. Hum Mol Genet. 2002;11(25):314556.

(4.) Moorhead PS, Nowell PC, Mellman WJ, Battips DM, Hungerford DA. Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res. 1960;20:613-6.

(5.) Seabright M. A rapid banding technique for human chromosomes. Lancet. 1971;2(7731):971-2.

(6.) Mitelman F. An International System for Human Cytogenetic Nomenclature. Basel: S. Karger Publishers; 2013.

(7.) Fitch N, de Saint Victor J, Richer CL, Pinsky L, Sitahal S. Premature menopause due to a small deletion in the long arm of the X chromosome: a report of three cases and a review. Am J Obstet Gynecol. 1982;142(8):968-72.

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(9.) Waters JJ, Campbell PL, Crocker AJ, Campbell CM. Phenotypic effects of balanced X-autosome translocations in females: a retrospective survey of 104 cases reported from UK laboratories. Hum Genet. 2001;108(4):318-27.

(10.) Vasu VR, Chandra N, Santhiya ST. X;7 translocation in an Indian woman with hypergonadotropic amenorrhea-a case report. Genet Test Mol Biomarkers. 2009;13(4):533-6.

(11.) Omrani MD, Saleh Gargari S, Azizi F. A de novo Reciprocal X; 9 Translocation in A Patient with Premature Ovarian Failure. Int J Fertil Steril. 2013; 7(2):130-3.

(12.) Chen CP, Lin SP, Chern SR, Kuo YL, Wu PS, Chen YT, et al. Array CGH characterization of an unbalanced X-autosome translocation associated with Xq27.2-qter deletion, 11q24.3-qter duplication and Xq22.3-q27.1 duplication in a girl with primary amenorrhea and mental retardation. Gene. 2014;535(1):88-92.

(13.) Sills ES, Cotter PD, Marron KD, Shkrobot LV, Walsh HM, Salem RD. Ovarian dysgenesis associated with an unbalanced X;6 translocation: first characterisation of reproductive anatomy and cytogenetic evaluation in partial trisomy 6 with breakpoints at Xq22 and 6p23. Mol Med Rep. 2012;5(1): 29-31.

(14.) Vitek WS, Pagidas K, Gu G, Pepperell JR, Simpson JL, Tantravahi U, et al. Xq;autosome translocation in POF: Xq27.2 deletion resulting in haploinsufficiency for SPANX. J Assist Reprod Genet. 2012;29(1):63-6.

Ananthapur Venkateshwari *, Avvari Srilekha, Koka Veena, Madireddy Sujatha, Akka Jyothy

--Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, India

* Corresponding Author: Ananthapur Venkateshwari, Department of Cell Biology, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad500 016, India


Received: Jul. 11, 2014

Accepted: Sept. 7, 2014

Table 1. Cases of balanced X; 1 translocations reported in

Sl. No    Reason for referral                Karyotype

1              Recurrent          46,X,t(X;1)(p22.1;p31) de novo

2          Development delay      46,X,t(X;1)(p22.1:p32) de novo

3              Learning          46,X,t(X;1)(p11.4;p36.3) de novo
         difficulties? Norrie

4         Multiple congenital         46,X,t(X;1)(q26;p22)mat
          Developmental delay

5        Mother: abnormal scan     46,X,t(X;1)(q26;p22) de novo
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Article Details
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Title Annotation:Case Report
Author:Venkateshwari, Ananthapur; Srilekha, Avvari; Veena, Koka; Sujatha, Madireddy; Jyothy, Akka
Publication:Journal of Reproduction and Infertility
Article Type:Clinical report
Geographic Code:9INDI
Date:Jul 1, 2015
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