engleski

Risk estimates in families with parental reciprocal translocations in comparison with outcome of pregnancies

Parental balanced reciprocal chromosome rearrangements (rcp) are among the major indications for chromosomal analysis of amniotic fluid cells. Because a very few reciprocal translocations have identical breakpoints, the accurate risk of unbalanced offspring at birth is difficult to obtain. By combining theoretical and empirical risk estimates (Daniel 1986, Stengel-Ruktowski et al 1988), as well as the segregation analysis of rcp in prenatal diagnosis data, we have analysed 45 Croatian families in order to compare the risk estimates with the actual outcome of pregnancies and to provide adequate information for genetic counselling of affected couples. Segregation analysis of 62 prenatal results revealed that 30 (48.4%) fetuses had normal karyotype, 24 (38.7%) were balanced carriers of rcp and 8 (12.9%) fetuses were unbalanced. The potential chromosomal imbalance in offspring of rcp heterozygotes was evaluated by measuring the chromosomal segments distal to the breakpoints (% of haploid autosomal length) and their length compared to the outcome of pregnancies. Empirical risk estimates showed that most of the rcp has a low (0-5%) risk of an unbalanced offspring. Eight (17.7%) of rcp were without risk and eight (17.7%) were medium risk (5-10%) translocations. Only two (4.4%) translocations had a high risk (>10%) for the birth of an unbalanced offspring. The average risk for the single segment imbalances was four times greater then the average risk for the double segment imbalances, 2:2/adj-1 being theoretically and empirically the most likely disjunction/segregation mechanism. The empirical risk estimates were in good agreement with the pedigrees of our families. This study confirms the fact that the risks for carriers of rcp depend on the disjunction/segregation mechanisms which are determined by the involved chromosomes and the breakpoint positions. The length of the segment imbalance is not an exclusive parameter in risk calculations, because the genetic content of the exchanged chromosome segments determines the survival probability as well. Therefore, an accurate analysis of the specific rcp, considering the sex and the age of the parental carrier must be performed in order to give more precise information to affected families.

risk; reciprocal translocations; carrier; pregnancy; outcome

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