Pericentric inversions

Summary A review is given of the incidence, cytogenetics, and biologic relevance of pericentric inversions (pii). In 251 cases in the literature and our patients, 96 different inversion forms with different breakpoints are found. Eighteen of these cases have been observed several times in unrelated families; they are classified as types. The problem of pii in the heterochromatic regions of chromosomes 1 and 9 is especially emphasized and the investigations required are pointed out.The significance of the individual pii is checked with regard to their behavior in meiosis and their phenotypical relevance. An approximately 1:1 segregation is found. Fertility, stillbirth, and rates of abortion are not statistically altered. The gonadal findings available at present in man are reported and commented on. The occurrence of aneusomic recombinants among the live offspring of carriers shows a marked dependence on the length of the relative inversion segments. Since these are distinctly below average in inversion types, they only result in recombinants in exceptional cases.Certain pointers to an above-random common occurrence of other chromosomal aberrations are not found in families with pii. A correlation between pii and clinical symptoms like-wise cannot be detected. However, in this connection it is pointed out that trisomic mosaics were observed jointly with pii (9) and pii (22). The review is completed by a brief examination of the literature concerning the significance of pii in evolution.     

Pericentric inversion of chromosome 19 in three families

Summary Pericentric inversion of chromosome 19 has been found in several members of three unrelated families from a restricted geographical region. In one of the families, an additional pericentric inversion of chromosome 9 was observed. Reproductive problems, multiple abortions in two families and a neonatal death in the third, were present. A review of previously described cases is included, and the genetic risk connected with this type of rearrangement is also discussed.     

Pericentric inversions: studies in 47 cases]

The authors report 47 cases of pericentric inversion. Eleven of them involve the chromosomes No. 2, 11 and 9. It appears that the risk of malformations and/or encephalopathy is obviously increased either by "position effect", aneusomie de recombinaison" or "interchromosomal effect". Prenatal diagnosis is therefore indicated. Thirty six cases involve the secondary constriction of chromosome No. 9. In such cases the risk is not enough increased to justify the prenatal diagnosis.     

Pericentric inversions of the X chromosome. A new observation and review of the published cases

A pericentric inversion of the X chromosome-inv(X) (p11.3q22) is transmitted in 3 generations. Male and female carriers are normal. The proposita is tetraplegic, severely retarded and suffers from general seizures. Grand mal seizures are known in the mother and grandmother. Different proportions of inactive X chromosomes in the proposita and the normal sister are discussed. The published cases of inv(X) are reviewed.     

Pericentric inversion of chromosome 12; a three family study

Summary A pericentric inversion of chromosome 12 has been followed in three large independently ascertained Danish families. Out of a total number of 52 persons examined, 25 were found to carry the inversion. The break-points in all three families were localized to p13 and q13, resulting in more than one-third of the total length of the chromosomes being inverted. However, no chromosomal aberrations arising because of meiotic crossing-over inside the inverted area have been found among the offspring of the carriers. The percentage of spontaneous abortions among carriers is found to be high, viz. 33%. The segregation rate is calculated to be 0.58, which is not significantly different from an expected segregation rate of 0.5. In family 3, an additional inversion of a chromosome 9 has been found in 4 individuals. Our results are discussed in relation to previous findings and with respect to the genetic counselling of families with pericentric inversions.     

Pericentric inversions in man: personal experience and review of the literature

Summary The Leuven cytogenetic centre experience on pericentric inversion in man is discussed with exclusion of the pericentric inversions of the heterochromatic blocks of chromosomes 1 and 9. In a total of 51,500 patients, referred for constitutional chromosome analysis during the period 1970–1985, pericentric inversions were found in 24 index patients. The breakpoints detected in these different pericentric inversions are summarized and compared to those found in previous reports. Bands 2p13, 2q21, 5q31, 6c21, 10q22, and 12q13 were shown to be repeatedly involved in the different studies and, furthermore, breakpoints at bands 2q11, 5p13, 5p15, 5q13, 7q11, 11q25, and 14p11 were present in this study as well as in our previous review on reciprocal autosomal translocations. In 13 familial pericentric inversions, even after exclusion of all inversion carrier probands, a 1.6:1 excess of pericentric inversion carriers versus karyotypically normal progeny was observed. While chromosomally unbalanced offspring represent 3.5% of all chromosomally investigated liveborns of the present study, 7.1% of all liveborn inversion carrier offspring presented with a mental retardation and/or multiple congenital anomalies (MR/MCA) problem. Additional chromosomal abnormalities, i.e. a 21 trisomy and an accessory small ring chromosome were observed in two pericentric inversion carriers. These data and results are discussed and compared to the data available in the literature.     

Pericentric inversion in chromosome 2 without phenotypic effect

A subject with pericentric inversion of chromosome 2: 46, XY, inv(2) (p11q13) is described. All the family members which present the same inversion are clinically normal     

Pericentric inversion in human chromosome 8 and spherocytosis

A cytogenetic study of a patient revealed a pericentric inversion in chromosome 8, and spherocytes in 10% of cells, in a routine blood smear. The critical portion which affected the expression of spherocytosis appeared to be localized at 8p22-8q21. The mother's karyotyping showed the transmission of the inversion to the child.     

Paracentric inversions in human chromosome 7

Summary A paracentric inversion (7)(q11q22) and mosaicism 46,XX/45,X was detected in a female with minor malformations. The same inversion was observed in the mother of the patient. The analysis of high resolution banded chromosmes revealed no visible imbalance in the inverted long arm of the chromosome 7. All published cases of paracentric inversions in the human chromosome 7 are reviewed and the relationship between this inversion and the occurrence of an aneuploidy of the sex chromosomes is discussed.     

Pericentric inversion of chromosome 2 (p11 q13) in unrelated families (author's transl)]

A pericentric inversion of chromosome 2 has been detected in 4 unrelated families. The break points are identical in band 2p11 and band 2q13. Reproductive history of these couples is analyzed. The pathology of these particular regions of chromosome 2 is discussed.     

Accommodating chromosome inversions in linkage analysis

This work develops a population-genetics model for polymorphic chromosome inversions. The model precisely describes how an inversion changes the nature of and approach to linkage equilibrium. The work also describes algorithms and software for allele-frequency estimation and linkage analysis in the presence of an inversion. The linkage algorithms implemented in the software package Mendel estimate recombination parameters and calculate the posterior probability that each pedigree member carries the inversion. Application of Mendel to eight Centre d'Etude du Polymorphisme Humain pedigrees in a region containing a common inversion on 8p23 illustrates its potential for providing more-precise estimates of the location of an unmapped marker or trait gene. Our expanded cytogenetic analysis of these families further identifies inversion carriers and increases the evidence of linkage.     

Pericentric inversion of chromosome 1 in three sterile brothers

Summary A pericentric inversion of chromosome 1 was found in three phenotypically normal brothers. The proband consulted for azoospermia. Also, one of his brothers is azoospermic and another one is severely oligozoospermic. G-banding studies indicate that the breakpoints of the inversion are at p13,q25.     

Whole arm inversions of chromosome 4 in Drosophila species

Inversions of genetic segments during the evolution of Drosophila are well documented in the X chromosome and most autosomes, but little attention has been paid to chromosome 4, the smallest autosome or "dot chromosome" present in many Drosophila species. From our previous mapping we have defined probes that mark proximal, intermediate, and distal locations of chromosome 4 in D. melanogaster. In situ hybridizations on salivary gland polytene chromosomes with these probes show that the whole right arm, including genes within cytological region 101EF-102F, is inverted relative to D. simulans. We also used these probes to determine the orientation of the arm of the dot chromosome in nine species of Drosophila, including eight from the melanogaster subfamily. To account for the observed whole arm inversions of chromosome 4 in five of the nine species examined, we propose that three inversion events have occurred during the evolution of these species. These whole arm inversions may explain some of the unusual features of this chromosome.     

The significance of pericentric inversions of chromosome 2

Summary Thirteen new cases of a pericentric inversion 2 collected from different laboratories are reported. In addition 41 cases of a pericentric inversion 2 were reviewed from the literature. The pooled data were analysed using Weinberg's proband method to evaluate the risk of a carrier for either children with congenital anomalies or reproductive wastage. In the corrected sample of 166 lifeborn offspring of carriers of a pericentric inversion 2 there were five who showed phenotypic anomalies and two died a few hours after delivery. The reported anomalies are heterogeneous and probably reflect the basic risk of any couple for abnormal lifeborn offspring. There has been no observation of a lifeborn who inherited an unbalanced recombination of a parental pericentric inversion 2. A carrier of a pericentric inversion 2 obviously has an increased risk for reproductive wastage. This is indicated by (1) an increase of the rate of spontaneous abortions and (2) an increase of the rate of index patients ascertained because of previous miscarriages. The risk of a carrier of a pericentric inversion 2 for a spontaneous abortion or a stillbirth may be about twice the basic risk of the general population.     

Familial pericentric and paracentric inversions of chromosome 1

Summary We investigated 33 individuals (21 carriers) from one family with a pericentric inversion involving a large part of chromosome 1 (1p36.11q32). In addition, we investigated 15 individuals (10 carriers) from another family with a paracentric inversion of a small part of chromosome 1(1p321p36.1). In each family, the index patient was ascertained because three miscarriages had occurred. Each carrier of these inversions was phenotypically normal. If the miscarriages of the index patients are excluded, the frequency of recognized miscarriages among the carriers of childbearing age was 9% (4 of 46) for the family with pericentric inversion and 17% (4 of 23) for the family with paracentric inversion. One of the pericentric inv(1) carriers had had a stillborn daughter. The carriers of the pericentric inversion who were of childbearing age had 41 children; carriers of the paracentric inversion who were of childbearing age had 19 children. No live-born children with birth defects were observed in either family. This evidence, together with the low frequency of miscarriages, suggests that crossover within the inversion loop occurs much less frequently than might be expected from the large size of this inversion. Our investigation suggests that the risk of recognized miscarriages, stillbirths, and live-born children with recombinant chromosomes who have birth defects may be much lower for inv(1) carriers than previously reported. The risk of having a malformed child because of a recombinant chromosome is probably less than 3% for carriers of the pericentric inversion and less than 6% for the carriers of the paracentric inversion.     

Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13.

The penetrance of the BRCA2 gene on chromosome 13q12-13 has been estimated in two large, systematically ascertained, linked families, by use of a maximum-likelihood method to incorporate both cancer-incidence data and 13q marker typings in the families. The cumulative risk of breast cancer in female gene carriers was estimated to be 59.8% by age 50 years (95% confidence interval [95% CI] 25.9%-78.5%) and 79.5% by age 70 years (95% CI 28.9%-97.5%). The cumulative risk of breast cancer in male carriers was estimated to be 6.3% (95% CI 1.4%-25.6%) by age 70 years. There was no evidence of any risk difference between the two families. These results indicate that the lifetime breast cancer risk in BRCA2 carriers, for at least a subset of mutations, is comparable to that for BRCA1. A significant excess of ovarian cancer in gene carriers was observed (relative risk 17.69, based on three cases), but the absolute risk of ovarian cancer was less than that reported for BRCA1. Significant excesses of laryngeal cancer (relative risk 7.67, based on two possible carriers) and prostate cancer (relative risk 2.89, based on five possible carriers) were also observed. One case of ocular melanoma, as well as a second eye cancer of unspecified histology, occurred in obligate gene carriers.     

Pericentric inversion of “fluorescent” segment in chromosome No. 3

During a short time span we identified 3 unrelated cases of pericentric inversion of the “fluorescent” segment in one chromosome No. 3. All 3 propositae were mentally defective female patients of a mental hospital; 1 case was familial with phenotypically normal father and grandfather.