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Prenatal diagnosis of PIBIDS
J B Savary1, F Vasseur, D Vinatier
1Laboratoire de Génétique Humaine, Pathologie Foetale (Pr. Deminatti), Faculté de Médecine, Lille, France.
Insights
This study identified a severe DNA excision repair defect in a child with PIBIDS (Pterygium, Intellectual disability, Polyplegia, Ichthyosis, Deafness, and Skeletal dysplasia). Prenatal diagnosis confirmed the defect in the fetus, leading to pregnancy termination.
Area of Science:
- Genetics
- Molecular Biology
- Biochemistry
Background:
- The study investigates a family with a documented history of PIBIDS (Pterygium, Intellectual disability, Polyplegia, Ichthyosis, Deafness, and Skeletal dysplasia).
- DNA excision repair mechanisms are crucial for maintaining genomic stability.
Purpose of the Study:
- To investigate DNA excision repair capacity in a patient diagnosed with PIBIDS.
- To establish prenatal diagnostic methods for PIBIDS based on DNA repair function.
Main Methods:
- Assessing DNA excision repair activity in lymphocytes using residual repair activity measurements.
- Quantifying UV-induced unscheduled DNA synthesis in amniotic fluid cells and fetal fibroblasts.
Main Results:
- The index case exhibited significantly reduced DNA excision repair activity (10.6-12.1%).
- Prenatal diagnosis in the fetus showed defective DNA repair (12.5-26.1%), consistent with PIBIDS.
- Post-termination fetal fibroblasts confirmed a severe DNA repair defect (9.2-13.5%).
Conclusions:
- A severe defect in DNA excision repair is a hallmark of PIBIDS.
- UV-induced unscheduled DNA synthesis is a reliable method for prenatal diagnosis of PIBIDS.
- Early diagnosis and genetic counseling are vital for affected families.
Abstract:
In a well-documented PIBIDS family, two investigations of DNA excision repair showed a severe defect in lymphocytes from the index case (residual repair activities were 10.6-12.1 per cent). The values for the mother, father, and sister were within the normal range when compared with a healthy control. In the pregnant mother, a prenatal diagnosis of PIBIDS was made by measuring UV-induced unscheduled DNA synthesis in cultivated amniotic fluid cells. Results ranged between 12.5 and 26.1 per cent depending on the UV doses applied and were consistent with an affected fetus. The parents opted for a termination of pregnancy. Following a therapeutic abortion, fetal skin fibroblasts were tested and showed a severe DNA excision-repair defect of 9.2-13.5 per cent of residual activity.