We report an unusual case of a balanced reciprocal translocation with a recombinant chromosome which has arisen from a familial balanced complex translocation. Fluorescence in situ hybridization studies were essential for the identification of the breakpoints. A review of 60 cases of balanced complex translocations (BCT) has revealed three cases similar to ours. Carriers of BCT have a high risk of having spontaneous abortions or a child with an unbalanced karyotype. Certain types of balanced rearrangements involving an insertion can give rise to a simpler balanced translocation as a result of crossover. Our observations support the assumption that the chance that a de novo balanced complex translocation is associated with an abnormal phenotype increases with the number of breakpoints.

This review examines the reproductive consequences for carriers of a balanced complex chromosome rearrangement (CCR). It is based on an analysis of CCRs in 103 adults referred for reproductive problems, including male infertility. The main focus is on reproductive risks based on data from 84 CCRs. Carriers of balanced CCRs have a high risk of an abortion and/or a chromosomally unbalanced child. I have identified roughly four different types of CCRs (I-IV); most (44%) belong to Type I with a simple 3-way or 4-way exchange of segments and risk factors similar to those for reciprocal translocations. There were only three CCRs (4%) of type II, which involve an inversion. Type III CCRs (21%) involve one or more insertions with ∼35% risk of a child with a duplication or a deletion of the inserted segment. Type IV CCRs (31%) involve a "middle segment" in a derivative chromosome with segments from at least three chromosomes. In ∼35% of these CCRs, recombination occurs in this segment, which can produce imbalance but in many cases it changes a CCR into a simpler balanced rearrangement in the next generation. Balanced CCRs, which have been often considered together in one group, can now be split into four types, each with a risk of a different type of imbalance. This analysis provides a better understanding of the reproductive consequences for carriers of balanced CCRs and should be useful in prenatal diagnosis and genetic counseling.

Objective To identify additional factors, such as maternal age or factors related to previous reproductive outcome or family history, and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages. Design Nested case-control study. Setting Six centres for clinical genetics in the Netherlands. Participants Couples referred for chromosome analysis after two or more miscarriages in 1992-2000; 279 carrier couples were marked as cases, and 428 non-carrier couples served as controls. Main outcome measures Independent factors influencing the probability of carrier status and the corresponding probability of carrier status. Results Four factors influencing the probability of carrier status could be identified: maternal age at second miscarriage, a history of three or more miscarriages, a history of two or more miscarriages in a brother or sister of either partner, and a history of two or more miscarriages in the parents of either partner. The calculated probability of carrier status in couples referred for chromosome analysis after two or more miscarriages varied between 0.5% and 10.2%. Conclusions The probability of carrier status in couples with two or more miscarriages is modified by additional factors. Selective chromosome analysis would result in a more appropriate referral policy, could decrease the annual number of chromosome analyses, and could therefore lower the costs.

This review of paracentric inversions in man includes what we know of the behaviour and reproductive consequences of paracentric inversions from other species. Observations of naturally occurring inversions in several species of plants and animals and results of experiments with mutagenically induced inversions in the mouse are discussed. From a review of 184 cases, it is concluded that most of the paracentric inversions in man are harmless and that the risk of heterozygotes having a child with an unbalanced karyotype is low. However, in some cases, it is difficult, if not impossible, to distinguish between a paracentric inversion and a paracentric insertion, the risk in the latter case being about 15%. Caution is also necessary in interpreting the results of prenatal diagnosis for heterozygotes of paracentric inversions, because of the possibility of a variety of unpredictable unbalanced chromosome products.

No abstract

We describe the phenotype of a child having a recombinant chromosome 3 with a duplication 3q13.2----q25 derived from a paternal inv ins(3)(p25.3q25q13.2). A review of 27 reported cases of intrachromosomal insertions has revealed that for a carrier of intrachromosomal insertion the risk of a child with an unbalanced karyotype is 15%. This risk may be higher for particular insertions. The recombinant chromosome can have a duplication or a deletion of different segments depending on whether the insertion is direct or inverted, paracentric or pericentric, and whether there is meiotic crossing over in the inserted or the interstitial non-inserted segment. Several of the insertions have been difficult to interpret and some of them have been mistaken for paracentric inversions. Caution is therefore indicated in interpreting parental karyotypes of a child with a deletion or a duplication, particularly if it is interstitial. This is because, whereas a risk of recurrence of a child with an unbalanced karyotype is low in de novo cases and for carriers of paracentric inversions, it is high for carriers of insertions.

The fact that techniques of prenatal diagnosis are used in India and China to selectively eliminate females is widely known. It has been extensively reported in the international media and in scientific publications since the 1990s. The publication of the Census of India 2011 shows that the ratio of girls to boys below the age of 6 years continues to decline at an alarming rate. Following that publication, this topic has again received international attention. The aim of this article is to better inform the human genetics community of the magnitude of this practice and its consequences in India.In this overview, we examine the impact of prenatal technology on the sex ratio in India. We present facts and figures from the Census of India and other publications that show that the practice is wide spread throughout India, in urban and rural areas, among the rich and the poor, and among the educated and the illiterate. We also briefly discuss the possible causes, consequences, and solutions.Genet Med 16 6, 425–432.

Reports of 107 cases (89 females and 18 males) with balanced X-autosome translocations and 11 cases with pericentric inversions (and their families) have been reviewed. Of the 78 informative females, 36 were infertile and had an X-breakpoint in the segment Xq13-26. Thus the existence of the critical segment has been amply confirmed by this review. However the finding of three normal fertile females with deletion of a part or the whole of this segment suggests that it is not the break in the critical segment, as was first thought, but rather the contact between loci in the critical segment and loci external to it that is responsible for the abnormal sexual phenotype. Six females were exceptions to the critical region hypothesis. The X-breakpoints in these were in the critical region and yet each had had one or more children. Three of the six women (two inversions and one translocation carriers) were not wholly normal as they suffered from menstrual cycle disorder, secondary sterility and/or early menopause. Four of the six (including the three true exceptions) had a breakpoint in band Xq22. It is possible that there are two critical segments within Xq13-26 separated by a small segment in band Xq22. Seven of the nine adult male carriers of the balanced X-autosome translocations were infertile. Even from this limited number of cases it appears that male carriers of X-autosome translocations are likely to suffer from a disturbance of spermatogenesis as is the case in mouse and drosophila. Male carriers of X-inversions do not necessarily suffer from infertility. Results from one family with X-inversion suggest that some sort of a position effect in the X affecting the sexual phenotype may also be operating in the male.