Autosomal Structural Abnormalities Research Articles

A systematic review and meta-analysis on the association between ICSI and chromosome abnormalities.

In the decade following the introduction of ICSI, a higher prevalence of de novo chromosome abnormalities, in particular sex chromosome and autosomal structural abnormalities, as well as inherited abnormalities was described in children conceived by ICSI compared to both naturally conceived (NC) children and children conceived by standard IVF. The explanation for the observed increase in prevalence is not clear and has been suggested to reflect parental factors (e.g. age or sperm quality) or to be a result of the ICSI procedure itself. Over the years, the procedure, as well as the patient group, and indications for ICSI treatment have changed. The objective of this systematic review and meta-analysis was to assess the prevalence of chromosome abnormalities in ICSI pregnancies and children and to examine any potentially increased risk compared to standard IVF and NC. Pubmed, Embase, Cochrane Libraries and Web of Science up to October 2020 were searched. Primary outcome measures were overall chromosome abnormalities and de novo abnormalities (including sex chromosome abnormalities and autosomal abnormalities). The secondary outcome was inherited abnormalities. We followed the PRISMA guidelines and relevant meta-analyses were performed. The search included 4648 articles, out of which 27 met the inclusion criteria, and 19 were included in quantitative synthesis (meta-analyses). The prevalence of chromosome abnormalities varied considerably between studies, possibly explained by large differences in sample size and patient demographics. Only five studies were eligible for pooled analyses on adjusted data. All studies had a critical risk of bias. Results from pooled adjusted data showed no evidence of an increased risk of overall chromosome abnormalities when comparing ICSI to either standard IVF (aOR 0.75 (95% CI 0.41-1.38)) or NC (aOR 1.29 (95% CI 0.69-2.43)). In contrast, meta-analyses on unadjusted data showed an increased risk of overall chromosome abnormalities in ICSI compared to both standard IVF (OR 1.42 (95% CI 1.09-1.85)) and NC (OR 2.46 (95% CI 1.52-3.99)) and an increased risk of de novo abnormalities in ICSI compared to NC (OR 2.62 (95% CI 2.07-3.31)). Yet, based on a very low certainty of evidence, the conclusion remains, that no indication of an increased risk of chromosome abnormalities in ICSI offspring could be found. If an increased risk of chromosome abnormalities in selected ICSI offspring should exist, the absolute risk continues to be small. This review provides an extensive overview of the existing evidence on the relationship between ICSI and chromosome abnormalities in the offspring. We highlight the need for well-designed large, prospective, controlled studies with systematic cytogenetic testing. Existing data are limited and, in many cases, marred by critical levels of bias.

Trisomy 9p. A brief clinical, diagnostic and therapeutic description.

Trisomy 9p is characterized by the partial or complete duplication of the short arm of chromosome 9. It is one of the most common autosomal structural abnormalities in newborn infants. This is a relatively poor gene region, so it may be more compatible with survival. It is characterized by delayed mental and psychomotor growth, craniofacial dysmorphisms, skeletal alterations, central nervous system abnormalities, congenital heart disease, and, to a lesser extent, kidney disorders. To establish a diagnosis, it is necessary to perform a cytogenetic study with G bands and, if available, fluorescence in situ hybridization complemented with comparative genomic hybridization for a better understanding of the genotype-phenotype correlation. Assessment should be interdisciplinary and encompassing a timely family genetic counseling, together with available therapeutic options in an early manner.

Chromosomal Abnormalities in Patients with Intellectual Disability: A 21-Year Retrospective Study

Background: Intellectual disability (ID) has been defined as a considerably reduced ability to understand new or complex information and to learn new skills. It is associated with life-long intellectual and adaptive functioning impairments that have a profound impact on individuals, families, and society. It affects about 3% of the general population. ID often comes out with other mental conditions like attention deficit, hyperactivity, and autism spectrum disorders (ASD), and it can be part of a malformation syndrome that affects other organs. It may be syndromic (S-ID) or non-syndromic (NS-ID). Objective: The aims of this study were to identify the profile of intellectually disable patients being referred for cytogenetic analysis in Morocco, to determine the prevalence of chromosomal abnormalities in a Moroccan group, and to compare the results with those of analogous studies from other countries. Participants: We included data from Moroccan patients with NS-ID and others with S-ID (mostly Down syndrome cases) who have been referred between 1996 and 2016. 1,626 patients were involved in this study, 1,200 were referred with a clinical diagnosis of Down syndrome, 37 were clinically diagnosed for ASD with ID, and 389 were suspected of NS-ID. Results: We identified 1,200 cases of Down syndrome. In 1,096 analyses (91.3%), a cytogenetic variant of trisomy 21 was identified: standard trisomy 21 in 1,037 cases (94.6%), a translocation in 34 cases (3.10%), and mosaicism in 25 cases (2.3%). The cytogenetic analysis among ASD with ID cases did not reveal any specific chromosomal abnormalities. The present study also shows that chromosomal abnormalities were present in 6.43% of the patients with NS-ID (25 abnormal karyotypes out of 389 NS-ID cases). Autosomal structural abnormalities were the largest proportion of chromosomal aberrations. Conclusion: The high rate of chromosomal abnormalities found in the Moroccan patients studied demonstrates the capital importance of cytogenetic evaluation in patients who show ID or any clinical development abnormality.

Outcome of fetuses with short femur length detected at second‐trimester anomaly scan: a national survey

To assess the relationship between the finding of fetal femur diaphysis length (FL) below the 5(th) percentile at the second-trimester scan and pregnancy outcome, in a population in which more than 90% of women attend first-trimester screening. This was a retrospective study of all Danish singleton pregnancies with a 17-22-week anomaly scan between 1 January 2008 and 30 June 2011. Information on FL and gestational age (GA) at anomaly scan, on birth weight and GA at delivery and on chromosomal abnormalities was obtained from the Danish Fetal Medicine Database. Short FL was identified in 2718 (1.8%) of 147,766 fetuses and was present in 11 (16.2%) of the 68 fetuses affected by trisomy 21 (positive likelihood ratio (LR+) 8.8 (95% CI, 5.1-15.2)). Trisomy 13/18 and unbalanced autosomal structural abnormalities were also associated with a short FL in three (12.0%, LR+ 6.5 (95% CI, 2.3-18.9)) and eight (32.0%, LR+ 17.4 (95% CI, 9.8-30.9)) of the cases, respectively. The risk of a fetus having trisomy 21, trisomy 18, trisomy 13 or an unbalanced autosomal structural abnormality was 1 : 123 (95% CI, 79-192), given a short FL. Pregnancies with a fetus with short FL were more often affected by early preterm delivery (before 34 weeks) (5.6%; odds ratio (OR) = 4.2 (95% CI, 3.5-4.9)) and small-for-gestational-age (SGA) infants (13.9%; OR = 4.3 (95% CI, 3.8-4.8)). Short FL at the second-trimester anomaly scan is associated with a significantly higher relative risk of chromosomal abnormalities, and a substantially higher absolute risk for SGA and early preterm delivery.

Chromosome abnormalities in Indonesian patients with short stature

BackgroundShort stature is associated with several disorders including wide variations of chromosomal disorders and single gene disorders. The objective of this report is to present the cytogenetic findings in Indonesian patients with short stature.MethodsG-banding and interphase/metaphase FISH were performed on short stature patients with and without other clinical features who were referred by clinicians all over Indonesia to our laboratory during the year 2003–2009.ResultsThe results of chromosomal analysis of ninety seven patients (mean age: 10.7 years old) were collected. The group of patients with other clinical features showed sex chromosome abnormalities in 45% (18/40) and autosomal abnormalities in 10% (4/40), whereas those with short stature only, 42.1% (24/57) had sex chromosome abnormalities and 1.75% (1/57) had autosomal abnormalities. The autosomal chromosomal abnormalities involved mostly subtelomeric regions. Results discrepancies between karyotype and FISH were found in 10 patients, including detection of low-level monosomy X mosaicism in 6 patients with normal karyotype, and detection of mosaic aneuploidy chromosome 18 in 1 patient with 45,XX,rob(13;14)(q10;q10).Statistical analysis showed no significant association between the groups and the type of chromosomal abnormalities.ConclusionChromosome abnormalities account for about 50% of the short stature patients. Wide variations of both sex and autosomal chromosomes abnormalities were detected in the study. Since three out of five patients had autosomal structural abnormalities involving the subtelomeric regions, thus in the future, subtelomeric FISH or even a more sensitive method such as genomic/SNP microarray is needed to confirm deletions of subtelomeric regions of chromosome 9, 11 and 18. Low-level mosaicism in normal karyotype patients indicates interphase FISH need to be routinely carried out in short stature patients as an adjunct to karyotyping.

Chromosome analysis by spectral karyotyping of spermatozoa from an oligoasthenozoospermic carrier of a 10; 21 reciprocal translocation

Cytogenetic analysis of germ-line cells prior to intracytoplasmic sperm injection (ICSI) treatment is thought to be necessary for infertile males with an identified chromosomal abnormality. We analyzed the chromosomal karyotype of human spermatozoa from an oligoasthenozoospermic carrier of a reciprocal translocation t(10; 21). Cytogenetic analysis of 39 spermatozoa was performed by spectral karyotyping (SKY) and by ICSI into mouse oocytes. The motile morphologically normal spermatozoa were injected into mouse oocytes. Of these spermatozoa, 38 (97.4%) were activated. Twenty-one (53.8%) of the activated oocytes formed two pronuclei. Metaphase chromosome spreads from 13 spermatozoa were analyzed. Only one spermatozoon was normal and 2 spermatozoa exhibited balanced translocation. Nine and one spermatozoa showed abnormalities related and unrelated to the translocation, respectively. The numbers of normal/balanced spermatozoa were lower than those in previous reports analyzing reciprocal translocations using a previously described technique involving penetrated golden hamster oocytes. After genetic counseling with the carrier and his partner, ICSI treatment was performed. Healthy female and male infants were delivered at 37 weeks gestation via a Caesarean section. The female infant was a carrier of the reciprocal translocation and the male infant was confirmed normal on prenatal diagnosis at 16 weeks gestation. For genetic counseling prior to ICSI treatment, the incidence of unbalanced type spermatozoa after swim-up or Percoll gradient treatment should be investigated and discussed with couples having fertility problems related to oligozoospermia autosomal structural abnormalities.

Chromosomal aberrations in couples undergoing intracytoplasmic sperm injection: influence on implantation and ongoing pregnancy rates

Objective: To determine the incidence of chromosomal aberrations in couples undergoing intracytoplasmic sperm injection (ICSI) and their influence on subsequent implantation and ongoing pregnancy rates. Design: Prospective study. Setting: Fertility center. Patient(s): Candidates for ICSI. Intervention(s): Chromosomes were trypsin-banded in 2,280 patients. In all cases, 10 metaphases were karyotyped. Sex chromosome analysis was performed in 10 additional metaphases. When apparent chromosomal aberrations were detected, 100 metaphases were analyzed. Main Outcome Measure(s): Implantation and ongoing pregnancy rates in couples with a chromosomal disorder. Results: A chromosomal abnormality was demonstrated in 7.2% of all couples. Among the male partners, 4.48% had aberrations. Autosomal aberrations were present in 2.96%, and numerical or structural sex chromosome abnormalities were found in 1.52%. Among the female partners, numerical or structural abnormalities were documented in 9.79%. Only 2.32% of the female partners had autosomal structural abnormalities. Numerical or structural anomalies involving sex chromosomes were found in 7.47%. Implantation rates of 9.4% and 16.3% per embryo were observed in female partners with sex chromosome mosaicism and autosomal aberrations, respectively. In male partners, the respective rates were 3.8% and 23.1%. Conclusion(s): The incidence of chromosomal disorders in couples seeking ICSI treatment is considerable, especially minor mosaicism (<10%) of sex chromosomes in the female partners. Preliminary data indicate a low implantation rate in couples with minor mosaicism of sex chromosomes.

Structural abnormalities of autosomal chromosomes in the male partner do not influence fertilization and early development of embryos after intracytoplasmic sperm injection.

The objective of this study was to determine whether or not abnormalities in the autosomal structure of the male partner have any influence on fertilization and early embryo development after intracytoplasmic sperm injection (ICSI). Thirty-seven couples in whom the male partners were examined by the same andrologist were included in this study. Six couples (group I) in whom the male partner possessed autosomal structural abnormality underwent seven ICSI cycles. As a control group, 31 couples (group II) in which the male partner was karyotypically normal underwent 41 ICSI cycles. Although the normal fertilization rates seen in group I were significantly higher than those in group II (P < 0.05), there was no significant difference in the cleavage rates between the two groups. We did not perform the analysis of the female partner's chromosomes, but we surmise that structural autosomal abnormalities in the male partner do not adversely influence fertilization at ICSI and early development of embryos.

Incidence and significance of chromosome mosaicism involving an autosomal structural abnormality diagnosed prenatally through amniocentesis: a collaborative study.

Among 179,663 prenatal diagnosis cases collected from ten institutions and two publications, 555 (0.3 per cent) were diagnosed as having chromosome mosaicism. Of these, 57 (10.3 per cent) were mosaic for an autosomal structural abnormality, 28 (5 per cent) for a sex chromosome structural abnormality, and 85 (15.3 per cent) were mosaic for a marker chromosome. Ninety-five cases of prenatally diagnosed mosaicism with a structural abnormality in an autosome and a normal cell line, and with a known phenotypic outcome, were collected for karyotype-phenotype correlations through our collaboration (40 cases), a prior survey (26 cases), and published reports (29 cases). They included 13 balanced reciprocal translocations, one unbalanced reciprocal translocation, four balanced Robertsonian translocations, four unbalanced Robertsonian translocations, four inversions, 17 deletions, three ring chromosomes, 19 i(20q), seven +i(12p), six other isochromosomes, and 17 partial trisomies resulting from a duplication or other rearrangement. All cases mosaic for a balanced structural rearrangement resulted in a normal phenotype. All cases of 46/46,i(20q) resulted in normal liveborns. Five of seven cases with 46/47,+i(12p) had an abnormal phenotype compatible with Killian-Pallister syndrome. The overall risk for an abnormal outcome for a mosaic case with an unbalanced structural abnormality, excluding 46/46,i(20q) and 46/47,+i(12p), is 40.4 per cent. In the same category, the study also suggested a correlation between the percentage of abnormal cells and an abnormal phenotype. For mosaicism involving a terminal deletion, the possibility of a familial fragile site should be considered.