Reciprocal chromosome translocations involving short arm of chromosome 9 as a risk factor of unfavorable pregnancy outcomes after meiotic malsegregation 2:2.

PURPOSE: Genetic counseling of carriers with individual chromosome translocation requires information on how balanced reciprocal chromosome translocations (RCT) will segregate, what possible form of unbalanced embryo/fetus/child can occur, and the survival rates that have been observed in the particular families. We collected new empirical data and evaluated pedigrees of RCT carriers involving 9p in order to improve risk figures. MATERIAL AND METHODS: Empirical data on 241 pregnancies of 70 carriers were collected from 32 pedigrees of carriers of RCT at risk for a single 9p segment imbalance (RCT9p) from the literature and unpublished data. The probability rates of particular types of pathology have been calculated according to the method of Stengel-Rutkowski and Stene. Cytogenetic interpretation was based on GTG, RBG and FISH techniques. RESULTS: The probability rate for unbalanced offspring at birth for the whole group of pedigrees was calculated as 17.8+/-3% (33/185) (high risk). Considering the size of the imbalanced segment of 9p, the probability rates for RCT carriers with a breakpoint position at 9p22 at 9p13 and at 9p11.2 were estimated separately, and were found as 21.2+/-4.4% (18/85), 25+/-8.8% (6/24) and 11.8+/-3.7% (9/76), respectively. For unbalanced fetuses at 2nd prenatal diagnosis, we found the risk value as 57.9+/-11.3 % (11/19). The risk value for unkaryotyped stillbirths/early deaths of newborns and miscarriages were 5.4+/-1.7% (10/185) (medium risk) and 13+/-2.8% (rate 24/185) (high risk) respectively. CONCLUSIONS: Our results showed that the recurrence probability rates are different for particular categories of unfavorable pregnancy outcomes. How much they are dependent on the size of 9p chromosome segments taking part in the imbalance needs further studies based on a larger number of observations.

Genetic counseling in carriers of reciprocal chromosomal translocations involving long arm of chromosome 16.

Families with balanced chromosomal changes ascertained by unbalanced progeny, miscarriages, or by chance are interested in their probability for unbalanced offspring and other unfavorable pregnancy outcomes. This is usually done based on the original data published by Stengel-Rutkowski et al. several decades ago. That data set has never been updated. It is particularly true for the subgroup with low number of observations, to which belong reciprocal chromosomal translocations (RCTs) with breakpoint in an interstitial segment of 16q. The 11 pedigrees from original data together with the new 18 pedigrees of RCT carriers at risk of single-segment imbalance detected among 100 pedigrees of RCT carriers with breakpoint position at 16q were used for re-evaluation of the probability estimation for unbalanced offspring at birth and at second trimester of prenatal diagnosis, published in 1988. The new probability rate for unbalanced offspring after 2 : 2 disjunction and adjacent-1 segregation for the total group of pedigrees was 4 +/- 3.9% (1/25). In addition, the probability estimate for unbalanced fetuses at second trimester of prenatal diagnosis was calculated as 2/11, i.e. 18.2 +/- 11.6%. The probability rates for miscarriages and stillbirths/early deaths were about 16 +/- 7.3% (4/25) and <2% (0/25), respectively. Considering different segment lengths of 16q, higher probability rate (0/8, i.e. <6.1%) for maternal RCT carriers at risk of distal 16q segment imbalance (shorter segment) was obtained in comparison with the rate (0/10, i.e. <4.8%) for RCT at risk of proximal segment imbalance (longer segment). It supports findings obtained from the original data for RCT with other chromosomes, where the probability for unbalanced offspring generally increased with decreasing length of the segments involved in RCT. Our results were applied for five new families with RCT involving 16q, namely three at risk of single-segment imbalance [t(8;16)(q24.3;q22)GTG, ish(wcp8+,wcp16+;wcp8-,wcp16+), t(11;16)(q25;q22)GTG, and t(11;16)(q25;q13)GTG] and two with RCT at risk of double-segment imbalance [t(16;19)(q13;q13.3)GTG, isht(16;19)(q13;q13.3) (D16Z3+,16QTEL013-D19S238E+,TEL19pR-; D16Z3-, D19S238E-,TEL19pR+), and t(16;20)(q11.1;q12)GTG, m ish,t(16;20)(wcp16+,wcp20+;wcp16+,wcp20+)]. They have been presented in details to illustrate how the available empiric data could be used in practice for genetic counseling.

[Genetic risk of families with t(1;2)(q42;q33) GTG, RHG, QFQ, FISH]. / Ryzyko genetyczne rodzin obciazonych translokacja chromosomowa t(1;2)(q42;q33) GTG, RHG, QFQ, FISH.

OBJECTIVES: A central concept in genetic counseling is the estimation of the probability of recurrence of unfavourable pregnancy outcomes (abortion, stillbirth and birth at malformed child). In case of chromosomal changes estimates are made on basis of segregation analyses in actual pedigree. If we have a few of pedigree members than risk estimate should be performed on basis combined our data and empiric data from literature. We present individual genetic risk for carriers of unique reciprocal translocation t(1;2)(q42;q33) detected through karyotyping of the patient with miscarriage. MATERIAL AND METHODS: The pedigree consisted 5 families of t(1;2)(q42;q33) carriers with 15 members of progeny was evaluated according to Stene and Stengel-Rutkowski. Cytogenetic analysis of persons of these families (7 persons) was performed on blood samples using GTG, RHG, QFQ and FISH techniques. Additional RCT pedigree analysis of Stengel-Rutkowski et at Collection, Polish Collection, Lituanian Collection, Bielorussian Collection and an available literature cases were performed. RESULTS: The translocation was classified as translocation at risk for double segment imbalances for trisomy 1q42-->qter together with monosomy 2q33-->qter or monosomy 1q42-->qter together with trisomy 2q33-->qter after 2:2 disjunction after adjacent-1 segregation of the meiotic chromosomes. Two improved risk values for RCT with segments 1q42-->qter, 2q33-->qter were obtained i.e. 6/44 (13.6% +/- 5.2%) and 4/20 (20% +/- 8.9%). The probability of occurrence for this translocation carriers was estimated as 7% (medium risk). On basis of direct analysis at presented pedigree a risk for miscarriage was estimated as 2/9. CONCLUSIONS: 1. Carrierships of t(1;2)(q42;q33) increased population risk value for unbalanced progeny at birth by 7% (medium risk) and for miscarriage 2/9. 2. Causative relation between presence of t(1;2)(q42;q33) and miscarriages is suggested. 3. Updated, new genetic risk values for RCT at risk for single segment 1q42-->qter imbalance is 6/44 (13.6% +/- 5.2%) at birth and for single segment 2q33-->qter imbalance is 4/20 (20% +/- 8.9%).

[Familial complex chromosome translocation of t(1;4;10)(q21.3;q27;q26.1) verified by FISH]. / Rodzinne wystepowanie zlozonej translokacji chromosomowej t (1;4;10) (q21.3;q27;q26.1) zweryfikowanej metoda FISH.

The inheritance complex chromosome translocation is a rare. A familial complex chromosome rearrangement t(1;4;10)(q21.3;q27;q26.1) involving three chromosomes ascertained due to four spontaneous abortions in phenotypically normal childless woman there is presented. Cytogenetic analysis according to classic banding techniques were verified by fluorescent in situ hybridization (FISH) technique.

[Pedigree analysis of childless families of reciprocal chromosome translocation carriers]. / Analiza rodowodowa bezdzietnych rodzin obciazonych nosicielstwem translokacji chromosomowych wzajemnych.

OBJECTIVES: Pedigree analysis of childless families of unique reciprocal chromosome translocation (RCT) carriers may be useful for clinical prognosis and genetic counselling. MATERIAL AND METHODS: The group 13 childless families of RCT carriers were detected. Cytogenetic analysis of RCT was performed on blood samples using GTG and RBG banding technique. RESULTS: Thirteen pedigrees were constructed on basis of 64 cytogenetic results and anamnestic data of 62 spontaneous abortions and 7 stillbirths. Familial RCT were found in ten families. In addition fourteen relatives of the RCT carriers have had healthy children. Further observations showed other three healthy children among progeny of eight families. Low risk for unbalanced progeny at birth were estimate in most families. CONCLUSION: Childless families of RCT carriers have possibility to have healthy offsprings. Spontaneous abortions are result of RCT carrierstrip.

[Jaeken's (CDG) syndrome in two sisters]. / Zespól Jaekena (CDG) u dwóch sióstr.

Jaeken's syndrome or the carbohydrate-deficient glycoprotein (CDG) syndrome, is a newly recognized metabolic syndrome with poor weight gain in children, and multisystematic abnormalities, mainly due to defective carbohydrate entities in many glycoproteins, leading to neurologic dysfunction. Using the standardized method of phenotype evaluation with computer assistance according to the Munich Dysmorphologic Database, two sisters with CDGs were examined to decide if this metabolic entity contains dysmorphic features characterising dysmorphic syndromes. Diagnosis was based on clinical symptomatology and transferrin isoforms which showed tetrasialotransferrin deficiency and increased disialotransferrin in serum. Dysmorphic studies can be helpful in recognition of this syndrome, now described for the first time in Poland.