Carrier Of Pericentric Inversion Research Articles

Higher chromosomal abnormality rate in blastocysts from a subset of patients with pericentric inversion (Inv) 1 variant

The purpose of this study was to evaluate the incidence of unbalanced chromosome rearrangement in blastocyst-stage embryos from carriers of pericentric inversion of chromosome 1 (PEI-1). A total of 98 embryos from 22 PEI-1 carriers were tested for unbalanced rearrangements, originating from inversion carriers, and overall aneuploidy. Logistic regression analysis indicated that the ratio of inverted segment size to chromosome length was a statistically significant risk factor for unbalanced chromosome rearrangement from PEI-1 carriers (p = 0.003). The optimal cut-off values to predict the risk of unbalanced chromosome rearrangement was 36%, with the incidence being 2.0% in the <36% group and 32.7% in the ≥36% group. The unbalanced embryo rate was 24.4% in male carriers compared to 12.3% in female carriers. Inter-chromosomal effect analysis was performed using 98 blastocysts from PEI-1 carriers and 116 blastocysts from age-matched controls. PEI-1 carriers had similar sporadic aneuploidy rates compared to those of age-matched controls at 32.7 vs. 31.9%, respectively. In conclusion, the risk of unbalanced chromosome rearrangement is affected by inverted segment size in PEI-1 carriers.

Pericentric inversion of chromosome 6 and male fertility problems.

As a significant chromosomal structural abnormality, chromosomal inversion is closely related to male infertility. For inversion carriers, the interchromosomal effect explains male infertility, but its specific mechanism remains unclear. Additionally, inversion carriers with different chromosomes have different clinical manifestations. Therefore, genetic counseling is difficult in clinical practice. Herein, four male carriers of pericentric inversion in chromosome 6 have been described. Two patients showed asthenospermia, one showed azoospermia, and the wife of the remaining patient had recurrent miscarriages. Through a literature search, the association between the breakpoint of pericentric inversion in chromosome 6 and male fertility problems are also discussed in this study. Overall, important genes related to asthenospermia in chromosome 6p21 were found, which may be related to the clinical phenotype. These results suggest that physicians should focus on the breakpoints of inversion in genetic counseling.

Clinical outcomes of Preimplantation genetic testing (PGT) application in couples with chromosomal inversion, a study in the Chinese Han population

BackgroundChromosomal inversion was considered to have adverse effects on pregnancy outcomes through abnormal gametogenesis. The purpose of this retrospective study was to investigate whether preimplantation genetic testing (PGT) improves pregnancy outcomes for couples with chromosomal inversion.MethodsA total of 188 cycles from 165 couples with one chromosomal inversion carrier were divided into two groups: PGT (136 cycles, 125 couples) and non-PGT (52 cycles, 50 couples). Biochemical pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage and live birth rates of their first transfer cycles, as well as cumulative live birth rates of each cycle and euploidy rates, were analyzed.ResultsThere were no statistically significant differences in the pregnancy outcomes between the two groups. The euploidy rate of pericentric inversion carriers was not higher than that of paracentric inversion carriers in PGT group (60.71% vs 50.54%, P = 0.073). Similarly, the euploid rate of male carriers was not higher than that of female carriers (61.2% vs 56.1%, P = 0.256).ConclusionsDue to limitation of retrospective study and small sample size, our current data showed that PGT cannot provide prominent benefits for inversion carriers in the Chinese Han population. Further prospective randomized controlled trials are needed to evaluate the effects of PGT.

Prenatal diagnostics in carrier of pericentric inversion of the chromosome 6

Two cases with different recombinant chromosomes associated with a paternal pericentric inversion inv(6) (p25q25.3) are presented. The data of ultrasound and cytogenetic studies, as well as the results of preimplantation genetic testing of embryos obtained in in vitro fertilization cycles are presented. Based on our own and published data, the possibility of the appearance of recombinant chromosomes in the progeny of inv(6)(p25q25.3) carrier is discussed.

Pericentric inversion in chromosome 1 and male infertility.

Pericentric inversion in chromosome 1 was thought to cause male infertility through spermatogenic impairment, regardless of the breakpoint position. However, carriers of pericentric inversion in chromosome 1 have been reported with normal fertility and familial transmission. Here, we report two cases of pericentric inversion in chromosome 1. One case was detected in utero via amniocentesis, and the other case was detected after the wife of the carrier experienced two spontaneous abortions within 5 years of marriage. Here, the effect of the breakpoint position of the inversion in chromosome 1 on male infertility is examined and compared with the published cases. The association between the breakpoint of pericentric inversion in chromosome 1 and spermatogenesis is also discussed. Overall, the results suggest that the breakpoint position deserves attention from physicians in genetic counseling as inversion carriers can produce offspring.

Генетический репродуктивный риск у носителей перицентрических инверсий

Перицентрические инверсии (ПИ) - это сбалансированные структурные хромосомные перестройки, частота которых в популяции варьирует от 0,12% до 0,7% [1]. Особенностью синапсиса и рекомбинации ПИ в мейозе является формирование инверсионной петли, единичный кроссинговер в которой может приводить к образованию рекомбинантных хромосом c дупликацией/делецией дистального по отношению к инверсии сегмента короткого плеча и делецией/дупликацией дистального сегмента длинного плеча соответственно. Клиническая значимость ПИ определяется риском формирования у носителя гамет (зигот) с хромосомным дисбалансом (ХД), приводящим к раннему спонтанному прерыванию беременности, мертворождению или рождению детей с пороками и/или аномалиями развития. Проведена оценка эмпирической частоты формирования сперматозоидов с рекомбинантными хромосомами, а также риска формирования гамет и выживаемости потенциальных зигот с ХД у четырех мужчин-носителей ПИ. Pericentric inversion are intrachromosomal balanced structural abnormalities. The frequency in the general population is ranged from about 0.12% to 0.7% [1]. To provide complete synapsis and recombination during meiosis pairing of the normal and inverted chromosomes requires the formation of inversion loop. One crossover within the inversion loop leads to the production of two complementary recombinant chromosomes with both duplicated and deleted chromosome segments including the regions distal to the inversion. The particular clinical relevance of inversion chromosomes is that they can set the stage for the generation of recombinant gametes that may lead to early miscarriages, stillbirth or congenital abnormalities. The estimation of empiric frequencies of recombinant spermatozoa, risk of abnormal gamete formation and potential zygote viability in four pericentric inversion carriers was performed.

57 - Characterization of a Complex Derivative Chromosome 18

We present an unbalanced potential recombinant chromosome 18 [46,XY,der(18)(qter->q22.3::p11.22->qter::?p11.2->pter)] that likely originated from multiple crossing over events during meiosis I from an ancestral balanced pericentric inversion of chromosome 18(p11.22q22.3). Cytogenetic analysis suggests that the distal short arm is retained at the 18q inversion break site along with the duplicated 18q22.2->qter region. The chromosome was detected in a fetus referred for prenatal diagnosis with abnormal ultrasound findings including lower urinary tract obstruction, oligohydramnios, and hypoplastic cerebellum. The derivative 18 chromosome was maternally inherited from a patient with learning disabilities, recurrent hiccups, partial hearing loss and aortic valve insufficiency. Maternal and prenatal microarray analysis detected an 8.64 Mb terminal duplication of 18q22.3->qter and an additional presumably unrelated 3.17 Mb microduplication at 22q11.21. The 18q duplication interval includes numerous OMIM genes. Although patients with intellectual disability carrying similar 18q duplications have been reported, the clinical phenotypes associated with terminal 18q duplications have not been well characterized in the literature. The 22q duplication is the meiotic reciprocal of the DiGeorge/VCF syndrome microdeletion region with phenotypes ranging from normal to affected with intellectual disability, developmental delay, and hypotonia . The combined clinical effects of these two duplications may be associated with a more severe variably expressed phenotype. The unusual structure of the derivative chromosome 18 may result in meiotic pairing problems beyond what is normally seen in pericentric inversion carriers. Inversion unbalanced recombinant risk increases with the distance between the breakpoints, and in this family there may be carriers of a presumed original inversion, as well as family members with this derivative chromosome 18 or more typical unbalanced recombinant chromosomes. FISH studies are in progress and a more detailed family history is being acquired to better characterize this chromosome.

DNA fragmentation and meiotic segregation in sperm of carriers of a chromosomal structural abnormality

To determine the meiotic segregation and DNA fragmentation in spermatozoa of carriers of a chromosomal structural abnormality. Case series. University hospital. Thirty-seven male carriers of a chromosomal structural abnormality (21 with a balanced reciprocal translocation, 7 with a robertsonian translocation, 9 with a pericentric inversion). Meiotic segregation was analyzed by the human sperm-hamster oocyte fusion technique or by fluorescent in situ hybridization, and DNA fragmentation was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Relationships between abnormal sperm parameters, DNA fragmentation, and meiotic mechanisms. The average rates of chromosomally unbalanced spermatozoa were 55.22%, 14.09%, and 18.43% for reciprocal translocation, robertsonian translocation, and pericentric inversion carriers, respectively. The rates of DNA fragmentation were significantly higher in the whole group of carriers of a chromosomal structural abnormality and in each specific group than in the control group. No correlations between sperm DNA fragmentation and parameters of spermogram, age, or percentage of unbalanced chromosomal gametes were found. The DNA fragmentation rate depends solely on the presence of a chromosomal structural abnormality, and, therefore, a chromosomal structural abnormality predicts DNA fragmentation. Both meiotic segregation and DNA fragmentation studies should be integrated in the genetic exploration of male carriers of a chromosomal structural abnormality.

Prenatal detection by subtelomeric FISH and MLPA of unbalanced meiotic recombinants resulting from parental pericentric inversions

Objective Pericentric inversion carriers are predisposed to produce unbalanced gametes that result in conceptuses having either a partial trisomy for one distal segment and a partial monosomy for the other or vice versa. Larger inversions result in smaller unbalanced distal segments and a higher likelihood of a viable fetus. In these cases the structure of the recombinant chromosome is similar to the original balanced inverted or normal ones despite the (unbalanced) genetic content. Such cases may not be detected prenatally by conventional cytogenetic analysis. Methods In all prenatal samples from the pericentric inversion carriers we applied subtelomeric FISH probes specific for the chromosome involved in order to detect parental meiotic recombinants resulting from a single cross-over event. Confirmatory MLPA was also applied in unbalanced fetuses. Results The occurrence of a duplication deficiency unbalance from pericentric inversion carriers was successfully detected in all three fetuses by FISH. MLPA assays applied in two cases confirmed these results. Conclusions The application of commercial FISH subtelomeric probes is a reliable method that could be routinely applied for the detection of single cross-over meiotic recombinants. MLPA is a sound alternative technique.

Meiotic segregation analysis in spermatozoa of pericentric inversion carriers using fluorescence in-situ hybridization

Pericentric inversions are structural chromosomal abnormalities resulting from two breaks, one on either side of the centromere, within the same chromosome, followed by 180 degrees rotation and reunion of the inverted segment. They can perturb spermatogenesis and lead to the production of unbalanced gametes through the formation of an inversion loop. We report here the analysis of the meiotic segregation in spermatozoa from six pericentric inversion carriers by multicolour fluorescence in-situ hybridization (FISH) and review the literature. The frequencies of the non-recombinant products (inversion or normal chromosomes) were 80% for the inv(20), 91.41% for the inv(12), 99.43% for the inv(2), 68.12% for the inv(1), 97% for the inv(8)(p12q21) and 60.94% for the inv(8)(p12q24.1). The meiotic segregation of 20 pericentric inversions (including ours) is now available. The frequency of unbalanced spermatozoa varies from 0 to 37.85%. The probability of a crossover within the inverted segment is affected by the chromosome and region involved, the length of the inverted segment and the location of the breakpoints. No recombinant chromosomes were produced when the inverted segment involved <30% of the chromosome length (independent of the size of the inverted segment). Between 30 and 50%, few recombinant chromosomes were produced, inducing a slightly increased risk of aneusomy of recombination in the offspring. The risk of aneusomy became very important when the inverted segment was >50% of the chromosome length. Studies on spermatozoa from inversion carriers help in the comprehension of the mechanisms of meiotic segregation. They should be integrated in the genetic exploration of the infertile men to give them a personalized risk assessment of unbalanced spermatozoa.

Pericentric inversion of chromosome 9: Prevalence in 300 Down syndrome families and molecular studies of nondisjunction

The incidence of Down syndrome (DS) families where one of the parents is an heterozygous carrier of pericentric inversion of the heterochromatic region of chromosome 9-inv(9) (qh) - was determined in 3 independent groups of 100 families each. The total number of 17 such families found in the sample is significantly greater than the expected number of 5.73 for a sample of non-DS families of equal size. Consequently, the statistical association of the presence of inv (9) (qh) in one parent with the birth of a DS offspring, and the correlative 3-fold increased risk of a DS child for such families, seem to be demonstrated. A study of the origin of nondisjunction, using restriction fragment length polymorphism (RFLP) segregation analysis with a sufficient number of chromosome 21 specific probes, has provided complete information in 7 of 8 available families. Although the statistical interpretation of the results is not straightforward, due to the small size of the sample, the observed data do not contradict the assumption that the presence of inv (9) (qh) in a parent increases, by a factor of about 3, the chance that the offspring will inherit an extra chromosome 21 from that parent. Nevertheless, gathering further data appears desirable because stronger evidence would have relevance both for clinical implications and for the understanding of the function of heterochromatin, particularly with respect to meiotic and mitotic processes.

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

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, 6q21, 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.

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The complete trisomy 9 is relatively rare due to high fetal mortality. He present here a malformed liveborn infant with a 47,XY, +9,inv(9)(p13;q13)mat karyotype. The infant presented:hydrocephalia,microphtalmia,small palpebral fissures,upward slanted eyes, ocular hypertelorism,broad base and prominent tip of the nose, low set posteriorly rotated malformed ears, micrognathia,incipient cleft lip,narrow and high arched palate,short neck,pterigium colli,narrow trunk,pectus excavatum,short limbs,hip dislocation, micropenis,criptorchidism,3rd phalange of 4th finger superposed over the 3rd and 2nd fingers in both hands,absent patella,joint limitation,and calcaneovalgus deformity. Death occurred two hours after birth. The post-mortem examination revealed:stenosis of aqueduct of Silvius,ventricular septal defect,left diaphragmatic hernia,marked bilateral pulmonary hypoplasia. The parental karyo-types revealed that the mother was a carrier of pericentric inversion of chromosome 9:inv(9)(p13;q13). Of the 6 liveborn infants with trisomy 9 previously reported in the literature,3 had also the same type of inverted chromosome 9,and one an enlarged 9qh+ segment,which were transmited from parental carries.In addition,these polimorphisms were also found to be associated with others cases of non-disjunction,such us:21,13,18 and 8.Although, these polimorphisms are considered non pathologic morphological variants,one wonders if during meiosis its presence is really so innocuo.