Indian Journal of Human Genetics Medknow Publications on behalf of Indian Society of Human Genetics ISSN: 0971-6866 EISSN: 1998-362x Vol. 8, Num. 1, 2002, pp. 32-33

Indian Journal of Human Genetics, Vol. 8, No. 1, Jan-Jun, 2002 pp. 32-33

Case Report

Fluorescence in Situ Hybridization Analysis of Balanced t (8;22) (q24.3;q12.2) in a Female with Recurrent Spontaneous Abortions

Babu Rao Vundinti, Lily kerketta, Seema Korgaonkar, Kanjaksha Ghosh, Dipika Mohanty

Institute of Immuno haematology (ICMR), 13th floor, New multistoryed building, K.E.M Hospital campus, Parel, Mumbai-12, India.
Address for correspondence: Dr. V. Babu Rao, Institute of Immuno Haematology (ICMR), 13th floor, New multistoryed building, K.E.M Hospital campus, Parel, Mumbai-12, India. E-mail: vbaburao@hotmail.com

Code Number: hg02008

Genetic counselling of couples with recurrent spontaneous abortions is among the most difficult areas in reproductive medicine. A large number of possible contributing factors responsible for recurrent miscarriages have been identified in recent years (Kumar, et al.1999). Participation of genetically imbalanced gametes in the process of fertilisation is a well recognised cause of recurrent spontaneous abortions. The imbalance may be familial or de novo and can be detected through the cytogenetic study of abortuses. Unbalanced gametes may also arise during meiosis when a balanced chromosome rearrangement is carried out by one of two apparently healthy parents. We report a balanced reciprocal translocation in a women with recurrent spontaneous abortions.

Case Report

A non- consaguineous couple (husband aged 38 years, wife aged 34 years) was referred for cytogenetic study due to multiple spontaneous abortions. The wife had five first trimister abortions. Her previous records showed no history of infections and hormonal imbalance. No anatomical abnormality was detected in ultrasonography of pelvis and abdomen.Cytogenetic study was carried out on maternal peripheral blood and products of conception of last pregnancy using GTG- banding. Maternal chromosomal analysis revealed 46, XX, t (8;22) (q24;q12) (Figure 1a) and the same chromosomal abnormality was detected in products of conception of last pregnancy. The husband chromosomal analysis found to be normal karyotype. Chromosomal analysis was also carried out in 10 individuals, (two generations) of maternal side and no chromosomal anomaly was detected.

Fluorescence in situ hybridization (FISH) was performed on maternal metaphases to detect accurate translocation break points. Three DNA probes, alphoid 8 (pZ8.4), 8q24.3 (bA125A), and 22q12.2 (bk99f11) (kind gift from Prof.M.Rocchi, University of Bari, Italy) were used in FISH. The nick-translation and hybridization were carried out using standard procedure. Centromeric and region specific 8q24.3 labelled with biotin and detected with Fluor X- dCTP (green). The 22q12.2 specific probe was labelled with CY3 (red). The slides were counter stained with DAPI. The images collected with CCD camera were elaborated with adobe photoshop. FISH analysis revealed, a reciprocal translocation at 8q24.3 and 22q12.2 regions (Figure 1b, see color plates).The chromosomes involved in the translocation are described as : der (8) (8p ter— : : 22q12.2— 22qter) and (22pter22q12.2q12.2 : : 8q24.3).

Discussion

The 8 and 22 chromosome involvement in the recurrent abortions and abnormal children have been reported (Godde-Salz et al. 1982 ; Walker, et al. 1995). The reciprocal translocation detected in the present case is a familial as products of conception showed the same chromosome anomaly.We believe that the history of multiple abortions in the present case, might be due to balanced reciprocal translocation in the mother.

Therotically, apart from the four different zygotes deriving from 2:2 nondisjunction, there are 20 different possibilities of zygotes deriving from 3:1 disjunction (Daniel 1979). With regard to the t (8;22) (q24.3;q12.2) most of the theoretically possible unbalanced karyotypes would be lethal. On the other hand, the duplication observed in the unbalanced offspring are not the only abnormal karyotype possible. For instance, trisomy 8, dup (8 q ter) and trisomy 22 are well described syndromes in live born infants might also occur.With regard to the case described here it has to be assumed that the normal and abnormal chromosome 8 have to pair together with the normal and the abnormal chromosomes 22 during pachetene. The pachetene configuration would be assymetric and could be the reason for 3:1 disjunction.

Three genes AEZ, NDRG1, and RECQLA present at 8q24.3 region and these are involved with the disease, acrodermatitis enteropathica, (Zinc deficiency type), neuropathy (hereditary motor and sensory tom type) and Rothmond-Thompson syndrome. Whereas 22q12.2 region genes are involved in the development of neurofibromatosis type-2, and meningioma related shcwannoma. However, there is a chance of live born children with the same tanslocation, transmitted from parents may develop abnormal phenotype and expression of genetic disease. Hence, apropriate genetic counselling is important to couples with translocation carriers and prenatal diagnosis is essential for the management of abnormal fetal development.

References

• Daniel A (1979). Structural differences in reciprocal translocations. Potential for a model of risk in reproduction. Hum Genet 51:171-182.
• Godde- Salz E, Oesinghaus S, Gorote W (1982). Meiotic segrgation in familial reciprocal translocation t (8q;22q). Am J Med Genet 11 : 241-247.
• Kumar KSD, Rao GNM, Kumari CK, Jyothy A (1999). Etiology of recurrent miscarriage: A review. Int J Obst Gynaecol India. 2: 25-34.
• Walker S, Howard P J, Hunter D (1985). Familial complex autosomal translocations involving chromosomes 7, 8, and 9 exhibiting male and female transmission with segregation and recombination. J Med Genet 22: 484-91.

Copyright 2002 - the Indian Society of Human Genetics

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