Recurrence risks for different pregnancy outcomes and meiotic segregation analysis of spermatozoa in carriers of t(1;11)(p36.22;q12.2)

Abstract

Cumulative data obtained from two relatively large pedigrees of a unique reciprocal chromosomal translocation (RCT) t(1;11)(p36.22;q12.2) ascertained by three miscarriages (pedigree 1) and the birth of newborn with hydrocephalus and myelomeningocele (pedigree 2) were used to estimate recurrence risks for different pregnancy outcomes. Submicroscopic molecular characterization by fluorescent in situ hybridization (FISH) of RCT break points in representative carriers showed similar rearrangements in both families. Meiotic segregation patterns after sperm analysis by three-color FISH of one male carrier showed all possible outcomes resulting from 2:2 and 3:1 segregations. On the basis of empirical survival data, we suggest that only one form of chromosome imbalance resulting in monosomy 1p36.22→pter with trisomy 11q12.2→qter may be observed in progeny at birth. Segregation analysis of these pedigrees was performed by the indirect method of Stengel-Rutkowski and showed that probability rate for malformed child at birth due to an unbalanced karyotype was 3/48 (6.2±3.5%) after ascertainment correction. The risk for stillbirths/early neonatal deaths was -/48 (<1.1%) and for miscarriages was 17/48 (35.4±6.9%). However, the probability rate for children with a normal phenotype at birth was 28/48 (58.3±7.1%). The results obtained from this study may be used to determine the risks for the various pregnancy outcomes for carriers of t(1;11)(p36.22;q12.2) and can be used for genetic counseling of carriers of this rearrangement.

Limited survivability of unbalanced progeny of carriers of a unique t(4;19)(p15.32;p13.3): a study in multiple generations

“…The frequencies of particular forms of unbalanced gametes produced by carriers of a balanced RCT are contingent on several factors including the size of chromosomal segments involved, their genetic content, sex of RCT carrier, and location of chromosome breakpoints. Survival of progeny with particular imbalances plus possibly other factors influence the risk estimation for the individual RCT carrier [ 5 , 32 , 33 ]. Therefore each empirical study is useful for genetic counseling.…”

Meiotic and pedigree segregation analyses in carriers of t(4;8)(p16;p23.1) differing in localization of breakpoint positions at 4p subband 4p16.3 and 4p16.1

“…These high probabilities rate for birth of child with chromosome imbalancy are not surprising. In general the relative high survival rates for progeny with imbalance of subterminal region of other involved chromosomes are observed in families of RCT carriers [ 2 , 7 , 19 ]. However, direct values of the probability rate for having children with unbalanced karyotype vary depending on the translocation (i.e., 18 %, compared to 42 %).…”

“…In general, published data presenting both pedigree analysis and meiotic segregation patterns of male RCT carriers involving other chromosomes are scarce [ 2 – 4 , 29 ]. However, in case of the lack of pedigree data, we may at least imply probabilities for birth child with balanced karyotype from the gamete meiotic segregation figures without risk of overestimating.…”

“…Clinical effects vary due to the different forms of the unbalanced gametes produced during the meiotic segregation of chromosomes involved in RCT. These different forms of unbalanced gametes can yield different survival rates of the unbalanced embryo, fetus, or child [ 1 , 2 ]. Knowledge of the meiotic patterns of segregation of RCT carriers, as compared to empirical data on segregation from pedigree analysis, may be useful in illustrating the natural selection of children due to various chromosomal imbalances in different prenatal and postnatal periods of development.…”

“…Knowledge of the meiotic patterns of segregation of RCT carriers, as compared to empirical data on segregation from pedigree analysis, may be useful in illustrating the natural selection of children due to various chromosomal imbalances in different prenatal and postnatal periods of development. Such results may prove valuable for genetic counseling of RCT carrier families [ 2 – 4 ]. The probabilities of different unfavorable pregnancy outcomes for carriers of particular RCTs—as determined from pedigree analyses—depend strongly on the type, size, and genetic content of unbalanced chromosomal segments involved in RCT [ 1 , 5 – 10 ].…”