Prenatal diagnosis of PIBIDS

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.

Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations

“…After a therapeutic abortion, the diagnosis was confirmed by severe DNA excision repair defect in fetal skin fibroblasts. While UV induced UDS cannot differentiate among different DNA repair abnormalities,11 this family had a previous child with diagnosed TTD 100. During a later pregnancy in the same reported family, prenatal diagnosis was made by chorionic villus sampling at 9 weeks gestation and finding quantitatively normal DNA excision repair 119.…”

“…Twenty-seven of the 47 patients with photosensitivity were reported as having mutations in XPD, one in XPB, and one in TTDA (table 3, fig 4). Four patients were not assigned to a complementation group, but were found to have cellular UV hypersensitivity 31 59 100. Although the XPD gene mutation has been reported to be associated with the clinical finding of photosensitivity, there was one case of a TTD patient112 with an XPD gene mutation reported as non-photosensitive.…”

“…Thirty-two of these patients (29%) were born prematurely (<37 weeks). Apgar scores were given for eight patients, two of which76 100 were <7 at 5 min, indicating perinatal asphyxia. Twenty-nine of the infants (26%) had a collodion membrane at birth.…”

“…Pre-eclampsia was reported in eight pregnancies (7%)22 32 39 68 94 100 105 115 and eclampsia or seizures in three 17 63 108. There did not seem to be a correlation between IUGR and pre-eclampsia, as only three cases had both 32 68 100. In addition, one pregnancy85 was reported as having an abnormal prenatal screening test (elevated maternal serum α-fetoprotein).…”

“…None of the pregnancies with the affected fetuses went to term. Methods of prenatal diagnosis reported included fetal hair biopsy and DNA repair measurements 90 98 100 118 119. One study measured UV induced unscheduled DNA synthesis (UDS) in cultivated amniotic fluid cells at 17 weeks gestation.…”