The authors have declared that no competing interests exist.
Recurrent pregnancy loss is an important reproductive issue with a heterogeneous etiology where two or more consecutive abortions occur before 20 weeks of gestation. Approximately 15% of all clinically recognized pregnancies result in miscarriage with an incidence of 1 in 300 cases. Couples, who experience repeated pregnancy loss before three months of gestation, mostly have fetuses with chromosomal aneuploids. A non-consanguineous couple with a married life of 4 years was referred to the Institute with a clinical history of three first trimester abortions. Karyotype analysis revealed a balanced autosomal translocation between chromosomes 4 and 6 with 46, XX, t (4;6)(q35; q22) karyotype in the female and normal 46, XY in the male partner. Therefore, the siblings and the couple were suggested for extended genetic counseling. Interestingly, similar translocation was seen in her father and three sisters, whereas her mother and elder sister showed a normal chromosomal constitution, indicating the paternal inheritance.
Embryonic or fetal demise is one of the most common outcome of conception where nature’s quality control works in selecting genetically normal offspring
The present case study reports a female with an inherited balanced translocation between chromosomes 4 and 6 at long arms of 35 and 22 breakpoints respectively.
A non-consanguineous couple with a complaint of RPL was referred to the institute. The age of the female was 24yr and male was 30 yr with a married life of 4 years. The clinical history of the couple showed three spontaneous abortions at the first trimester. The pedigree analysis shows that the female has four siblings and no brothers whereas the male partner has one sister and one brother who are fertile (
Cytogenetic analysis of peripheral blood lymphocytes of the couple was performed according to Moorehead et al. (1960) protocol, and standard GTG-banding was done
Karyotype analysis revealed a balanced autosomal translocation between chromosomes 4 and 6 with 46, XX, t(4;6)(q35; q22) chromosomal constitution in the female partner and a normal karyotype of 46, XY in the male partner (
Couples with balanced translocations usually have a normal phenotype but may have infertility associated with oligospermia in males and miscarriages in females. This is because of the risk of producing unbalanced gametes that gets terminated before reaching the second trimester.
The present case reported a female partner with a history of abortions revealed 46, XX, t(4;6)(q35; q22) karyotype. The inheritance of such translocation may increase the risk of miscarriages due to mutation or segregation in the previous generations and or also influenced by the size and the genetic content of the rearranged genetic segment in the present generation or in some cases it may be a novel translocation. There are only a few reports in the literature associated with abnormalities in either chromosome 4 or chromosome 6. An earlier study by Neri et al. (1980), reported a balanced translocation between chromosomes 4 and 9 t (4;9) (q35;q12) with a breakpoint within the heterochromatic region of chromosome 9 in a woman with recurrent abortions
Similarly, previous reports have indicated a correlation between the breakpoints at 4q13, 4q21, 4q25, 4q32, and 4q35 with recurrent abortions and reproductive failures
Another gene from protein tyrosine phosphatase family, PTPRK, which is mapped to 6q22.2-23.1 encodes protein tyrosine phosphatases (PTPs) that regulate cell growth, differentiation, mitotic cycle, and oncogenic transformation during the development. LAMA2 another gene extends from 6q22-q23, encodes Laminin, an extracellular protein which is a major component of the basement membrane. Laminin helps to mediate the attachment, migration, and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components
As there is a crucial role of chromosomal anomalies in first-trimester pregnancy loss, all the couples who encounter RPL should be evaluated for the cytogenetic abnormalities. Further, the carriers of chromosomal translocation with pre-gestational or gestational infertility should be counseled on chromosomal breakpoints and the various technologies available for assisted reproduction. A pre-implantation genetic diagnosis can be suggested for couples who are at risk of transmitting a genetic disease or structural chromosomal abnormality to their offspring. All the siblings who inherited the balanced translocation were given extended genetic counseling.
Authors thank Department of Biotechnology, New Delhi, India for financial support.