A unique 7p/12q chromosomal abnormality associated with recurrent abortion and hypofibrinogenemia

by Selleckchem | Jun 10 2023

Recurrent first trimester abortions led to evaluation of a 25-year-old woman. Studies revealed she had hypofibrinogenemia (68 mg/dL) without evidence of dysfibrinogenemia or increased fibrinogen turnover. She was also found to have a unique 46,XX, t(7;12) (p 15.2;q24.31) karyotype. Hypofibrinogenemia and identical chromosomal abnormalities were found in other members of her kindred. Southern blots of genomic DNA from the patient, her mother, and her daughter hybridized to human fibrinogen probes showed alpha, beta, and gamma fibrinogen genes to be present and without structural alterations when compared to normal controls. We conclude that the chromosomal abnormality and the hypofibrinogenemia are related but in an unclear manner. Because fibrinogen infusion in the proposita was associated with successful gestation, we also concluded that the chromosomal abnormality itself was not responsible for the repeated abortions but that fibrinogen concentration may be critical in securing implantation.

Comments:

Based on the information provided, the 25-year-old woman has recurrent first-trimester abortions and is evaluated for the underlying cause. The evaluation reveals that she has hypofibrinogenemia, a condition characterized by low levels of fibrinogen in the blood, without any evidence of dysfibrinogenemia (abnormal fibrinogen structure) or increased fibrinogen turnover (excessive breakdown of fibrinogen). Additionally, she has a unique chromosomal abnormality, specifically a balanced translocation between chromosomes 7 and 12 (designated as t(7;12)(p15.2;q24.31)), which is also found in other affected members of her family.

Southern blot analysis, a technique used to study DNA sequences, was performed on the patient, her mother, and her daughter using human fibrinogen probes. The results showed that the alpha, beta, and gamma fibrinogen genes were present and structurally intact, similar to normal controls. This suggests that the observed hypofibrinogenemia is not due to any alterations or abnormalities in the fibrinogen genes themselves.

The relationship between the chromosomal abnormality and the hypofibrinogenemia is unclear based on the information provided. Although both conditions are present in the patient and her affected relatives, the exact mechanism linking them is unknown.

Notably, the administration of fibrinogen infusion to the patient during pregnancy was associated with successful gestation, implying that low fibrinogen levels might have contributed to the previous pregnancy losses. This suggests that maintaining an adequate fibrinogen concentration could be critical for successful implantation and preventing miscarriages in this particular case.

In summary, the woman's recurrent first-trimester abortions are associated with hypofibrinogenemia and a unique chromosomal abnormality (t(7;12)). The precise relationship between these two conditions remains unclear, but the successful outcome of pregnancy following fibrinogen infusion suggests that maintaining adequate fibrinogen levels may play a role in ensuring successful implantation. Further investigation and genetic counseling may be warranted for the affected family members.