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Biomedical subjects

J Stene

Publications and source records attributed to J Stene.

At least 19 recordsLinked to original sources
PubMed1992

Experiences with risk estimates for carriers of chromosomal reciprocal translocations.

The risk estimates for individual carriers of ten different familial reciprocal translocations detected among 500 couples with reproductive failures are presented. These were established by application of the empirical data analysed by Stengel-Rutkowski et al. (1988) and the guidelines given in Stene & Stengel-Rutkowski (1988). Different risks were estimated for unbalanced offspring at birth or at second trimester prenatal diagnosis for abortions, or stillbirths/early deaths. These risk estimates varied considerably from translocation to translocation. Carriers of five translocations had risks for offspring with single-segment imbalances. The birth risk figures ranged from 0.1% to 13.8%. Carriers of five other translocations had risks for double-segment imbalances with birth risks ranging from 0% to 3.2%. The estimated risk figures were independent of the method of ascertainment. Among the parents of the index cases we found nine maternal carriers and only one paternal carrier. This presentation illustrates the need for individual risk counselling of each carrier with reciprocal translocation regarding further family planning.

Abortion, Spontaneous↗
PubMed1989

Comments on estimations of risks to translocation carriers.

Two projects for estimation of risks to carriers of reciprocal translocations based on data from more than 1,100 families are compared. The 2 projects differ considerably with regard to the amount of information utilized in the data, the statistical methods used--either standard computer programs or methods specially developed for the data--and the relevance and variety of the obtained results. The comparison shows the strength of utilizing tailor-made statistical methods for extracting relevant information from available data in human genetics instead of statistical standard methods from general computer programs.

Congenital Abnormalities↗
PubMed1989

The incomplete, multiple ascertainment model: assumptions, applications, and alternative models.

Assumptions and applications of the widely used incomplete, multiple ascertainment model have been examined. The common use of a reduced version of the model by suppressing the information about independently ascertained probands leads to inaccurate and unstable estimates. The fact that many samples consist mainly of families ascertained through the first member who has the disorder may lead to seriously biased estimates of the segregation probability, as the model does not take this common ascertainment situation into account.

Child↗
PubMed1987

A reanalysis of the New York State prenatal diagnosis data on Down's syndrome and paternal age effects.

This paper reanalyzes the data from the Hook and Cross (1982) paper in this journal concerning the association between Down's syndrome and paternal age. The New York State (NYS) data are compared with a large European collaborative study by Ferguson-Smith and Yates (1984). The maternal-age-dependent risks in the NYS data were found to be significantly higher than in the European data. When the NYS data was divided into three groups by means of the paternal age, a marked two-peaked distribution was found. The maternal-age-dependent risk was high when the fathers were up to 33 years old, low when the fathers' ages were 34-39 years and high again when the fathers were at least 40 years old. The differences were significant. The results speak in favour of the existence of temporal, geographic, or environmental variations in the risk for de novo trisomy 21, as well as of a paternal age effect. The existence of a "paternal age effect" in at least some populations is confirmed. If the results of this paper are confirmed in other investigations, it will be necessary to revise present genetic counselling rules towards far more individually specified considerations.

Adult↗
PubMed1986

Comments on methods and results in: Sherman et al., "Segregation analysis of balanced pericentric inversions in pedigree data".

The analysis by Sherman et al. (1986), its basis and results have been examined. The analysis relies on general methods, which may give acceptable results under the special conditions considered by the authors, but will usually produce more or less misleading results. The program POINTER (Lalouel & Morton 1981) is shown to be based partly on a chain of irrelevant arguments for the actual context. The so-called "conventional ascertainment rules" (Morton et al. 1983) are shown to produce misleading results in cases where their assumptions are not satisfied. The mean risk for unbalanced offspring is underestimated because of an erroneous ascertainment correction. The segregation frequencies are found to be different in three national samples, contrary to the claim by Sherman et al. Only a small proportion of all information available in the data has been utilized. Alternative and more appropriate models, hypotheses and procedures have been suggested. The frequent use of packages with computer programmes of standard statistical procedures in nonstandard situations with data from collaborative studies in human cytogenetics is discussed.

Chromosome Inversion↗
PubMed1984

Risk for chromosome abnormality at amniocentesis following a child with a non-inherited chromosome aberration. A European Collaborative Study on Prenatal Diagnoses 1981.

Based on 2890 prenatal diagnoses from 12 European countries the risk for a chromosomally abnormal fetus at amniocentesis after the birth of a child with a chromosome abnormality has been estimated to be 1.3 per cent when the mother's age is 34 years or less at amniocentesis and 1.8 per cent if the mother is older. This risk does not depend on paternal age, and it is independent of the type of the chromosome abnormality of the index child. Some geographical heterogeneities were detected. Therefore, the overall risk has to be considered as a rough estimate. The chromosome constitution of the abnormal fetus differed from that of the index patient in 21 of 41 cases. Several explanations for the higher risk have been discussed. If the index child had trisomy 18, 13 or a sex chromosome abnormality, the fetus tended to be a female. If the index child was a trisomy 21, the fetal sex ratio was normal.

Adult↗
PubMed1984

Familial Wolf's syndrome with a hidden 4p deletion by translocation of an 8p segment. Unbalanced inheritance from a maternal translocation (4;8)(p15.3;p22). Case report, review and risk estimates.

This is the case report of a patient with Wolf's syndrome having a monosomy 4pter----p15.3 and an additional trisomy 8pter----p22, derived from a maternal balanced translocation t(4;8)(p15.3;p22) after 2:2 disjunction and adjacent-1 segregation. The patient's phenotype is presumably slightly modified by the trisomic 8p segment. Literature analyses indicate that phenotypic "hybrids" with traits of monosomy 4p and of other autosomal segment trisomies exist. The dermatoglyphics of the patient were not highly characteristic for Wolf's syndrome. Also the dermatoglyphics of the balanced translocation carriers were unspecific and did not reflect the carrier status. Pedigree analyses of 46 reported families with reciprocal translocations involving the short arm of chromosome 4 show a high risk (20.5% +/- 4.6%) for unbalanced offspring (trisomy or monosomy 4p) after 2:2 disjunction and adjacent-1 segregation, if the breakpoint in the recipient chromosome is terminal and the resulting imbalance concerns the 4p segment only. It is considerably lower (4.5% +/- 2.5%) if the breakpoint in the recipient chromosome is subterminal, as in the reported case, and the resulting imbalance concerns other chromosome segments additionally to the 4p segment. In both instances, the risk decreases with increasing segment length. The risk for unidentified abortions, stillbirths or neonatal deaths is also high in these families (about 40%). The frequency of progeny with balanced compared to progeny with normal karyotype corresponds to the expected 50% for alternate segregation.

Abnormalities, Multiple↗
PubMed1984

Linkage studies in Menkes' disease. The Xg blood group system and C-banding of the X chromosome.

Menkes' disease is a rare, genetically determined disturbance of copper metabolism which is transmitted as an X-linked recessive character. By comparative gene mapping it can be suggested that the most likely localization of the gene for Menkes' disease is on the long arm of the human X chromosome close to band q 13. This regional assignment is supported by the present analysis of the genetic relationship between the Menkes locus, the Xg locus, and the centromere in five Danish families. The evidence suggests close linkage between the Menkes locus and the centromere. The most likely value of the recombination fraction is 0.05 and the maximum lod score is above the conventional +3 limit. Linkage analysis of the Menkes locus and the Xg locus showed a recombination value of 0.24, but the maximum conditional score is 0.28, which is far below the conventional +3 limit. The present study demonstrates a successful application of a chromosomal morphological marker in linkage analysis and carrier detection of a single gene disorder. The close linkage between the gene for Menkes' disease and the centromere region was used to improve the classification of several females in whom the copper uptake into cultured fibroblasts was either inconclusive or not available.

Blood Group Antigens↗
PubMed1982

Genetic risks for familial reciprocal translocations with special emphasis on those leading to 9p, 10p and 12p trisomies.

An analysis of genetic risks for reciprocal translocations is given. Data from translocation families, ascertained through unbalanced offspring with trisomy 9p, 10p and 12p, were taken from the literature. The translocations were specified according to (1) the type of trisomy, (2) the degree of resulting chromosomal imbalance (partial short arm trisomies, complete short arm trisomies, complete short arm trisomies including long arm segments) and (3) the type of disjunction (2:2 or 3:1) and segregation (adjacent-1, adjacent-2; tertiary trisomy, interchange trisomy). The risks for unbalanced liveborn offspring were high for translocations leading to partial short arm trisomies through 2:2 disjunction and adjacent-1 segregation (25-29%). They were lower for translocations leading to complete short arm trisomies through the same disjunction/segregation mechanism (5-17%). Low risks were obtained for translocations, leading through 3:1 disjunction to unbalanced offspring (about 2%). For 2:2 disjunction and adjacent-2 segregation and for 3:1 disjunction the risk is significantly lower for male than for female carriers.--The frequency of balanced karyotypes compared with normal karyotypes deviated among the phenotypically normal offspring of parental carriers from the theoretical 1:1 ratio, both for translocations ascertained through trisomy 12p and trisomy 10p.--It was demonstrated that the genetic risk for reciprocal translocations depends exclusively on (1) the degree of possibly resulting genetic imbalance and (2) the probability of the disjunction/segregation mechanism leading to this type of imbalance. Both factors can be predicted from the position of breakpoints.--The precision of breakpoint localizations and its impact on the risk estimation are also considered.--Finally, general rules for genetic counselling of families with reciprocal translocations are indicated.

Age Factors↗
PubMed1981

Paternal age and Down's syndrome: data from prenatal diagnoses (DFG).

From prenatal diagnosis data obtained on mothers aged 35 years and above in the Federal Republic of Germany (DFG data), older fathers are demonstrated to have an increased risk of having trisomy 21 offspring. For paternal ages of 41 years upward, the age effect is quite strong. The risk for a fetus to have any de novo chromosomal aberration increases more with advancing paternal age for older mothers than for younger ones. Thus the ages of both parents have to be taken into account as an indication for prenatal diagnosis. Risk figures for trisomy 21 and for any de novo chromosomal aberration are given, together with preliminary recommendations for prenatal diagnosis for different combinations of parental ages.

Adult↗
PubMed1981

New chromosomal dysmorphic syndromes. 4. Trisomy 12p.

This is the report of two independent families in which a balanced maternal translocation led to trisomy 12 p in one of each their offspring. Evaluation of 21 further case reports indicates that this is a phenotypically well defined syndrome which leads to severe developmental retardation. It can be recognized by a characteristic combination of craniofacial anomalies which are summarized in a phantom picture. The gene sequences which produce the typical features in the trisomic state must be localized distally to band 12p12, which is the breakpoint in the partial trisomies. The specific craniofacial anomalies are not visibly modified by the length of the trisomic segment or additional small monosomies or trisomies of recipient chromosomes. However, the frequency and severity of organ malformations and the resulting probability of survival seem to decrease with increasing degrees of chromosomal imbalance. A cytogenetic classification of the 21 inherited translocations and a segregation analysis from the pedigree data was performed. For the different types of translocations the calculated risk figures are given.

Chromosomes, Human, 6-12 and X↗
PubMed1980

[Prenatal diagnosis in parents with a balanced structural chromosome aberration (author's transl)].

By means of 10 case reports, the significance of prenatal diagnosis and the risk for the progeny of parents with a balanced structural chromosomal aberration are demonstrated. The aberrations were ascertained through: a previous malformed child, previous miscarriages or stillbirths or through fetal cell analysis during prenatal diagnosis performed for independent reasons. Theoretical considerations concerning the estimates of risk figures in these families are presented and the currently available risk values which are the basis of the indication for prenatal diagnosis, given.

Adult↗
PubMed1979

Choice of ascertainment model II. Discrimination between multi-proband models by means of birth order data.

Probability models have been developed for family data, where each family has been selected or ascertained through a group of m probands, where m is a known parameter, not a random variable. The birth orders of the probands among the affected children are reported for each family. It is demonstrated that this information is sufficient for choice of ascertainment model. The conditional probability that an ascertained family with s children has r affected ones, depends, in addition to the segregation parameter, on the birth order of the youngest proband only. By means of the joint distribution of the birth orders of the other probands, it can be demonstrated if the ascertainment takes place through affected children near to or distant from each other in relative birth orders. Statistical methods have been developed for cases with two and cases with m probands.

Birth Order↗