Supernumerary Marker Chromosome Research Articles

Genetic analysis and assisted reproductive guidance for two infertile patients with rare small supernumerary marker chromosomes

To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC). Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47,XY,del(16)(p10p12),+mar[65]/46,XY,del(16)(p10p12)[6]/48,XY,del(16)(p10p12),+2mar[3].ish mar(Tel 16p-,Tel 16q-,CEP 16-,WCP 16+). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47,XX,+mar[37]/46,XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5:g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.

Prenatal diagnosis of fetuses with absent/hypoplastic nasal bone in second-trimester using chromosomal microarray analysis.

Pathogenic copy number variants (pCNVs) are associated with fetal ultrasound anomalies, which can be efficiently identified through chromosomal microarray analysis (CMA). The primary objective of the present study was to enhance understanding of the genotype-phenotype correlation in fetuses exhibiting absent or hypoplastic nasal bones using CMA. Enrolled in the present study were 94 cases of fetuses with absent/hypoplastic nasal bone, which were divided into an isolated absent/hypoplastic nasal bone group (n = 49) and a non-isolated group (n = 45). All pregnant women enrolled in the study underwent karyotype analysis and CMA to assess chromosomal abnormalities in the fetuses. Karyotype analysis and CMA detection were successfully performed in all cases. The results of karyotype and CMA indicate the presence of 11 cases of chromosome aneuploidy, with trisomy 21 being the most prevalent among them. A small supernumerary marker chromosome (sSMC) detected by karyotype analysis was further interpreted as a pCNV by CMA. Additionally, CMA detection elicited three cases of pCNVs, despite normal findings in their karyotype analysis results. Among them, one case of Roche translocation was identified to be a UPD in chromosome 15 with a low proportion of trisomy 15. Further, a significant difference in the detection rate of pCNVs was observed between non-isolated and isolated absent/hypoplastic nasal bone (24.44% vs. 8.16%, p < .05). The present study enhances the utility of CMA in diagnosing the etiology of absent or hypoplastic nasal bone in fetuses. Further, isolated cases of absent or hypoplastic nasal bone strongly suggest the presence of chromosomal abnormalities, necessitating genetic evaluation through CMA.

Cytogenomic characterization of small supernumerary marker chromosomes in patients with pigmentary mosaicism.

The combination of gene content on the marker chromosome, chromosomal origin, level of mosaicism, origin mechanism (chromothripsis), and uniparental disomy can influence the final characterization of sSMCs. Several chromosomal aberrations, including sSMCs, have been observed in 30%-60% of patients with pigmentary mosaicism, and in more than 80%, chromosomal abnormalities are present in the mosaic state. In patients with pigmentary mosaicism the most representative chromosomes involved in sSMCs are 3, 5, 6, 9, 10, 13, 15, 18, 20, and X. In this study, we included the complete clinical, cytogenetic, and molecular characterization of seven patients with pigmentary mosaicism associated with the presence of SMCs of different chromosomal origins. The patients were diagnosed by the Genetics and Dermatology Department of three different hospitals. Cytogenetic and FISH analyses were performed on peripheral blood, light skin, and dark skin. FISH analysis was performed using different probes, depending on the marker chromosome description. Different array analysis was performed. To date, of the seven cases studied, the chromosomal origins of six were successfully identified by FISH or array analysis. The chromosomes involved in SMCs were 6, 9, 15, and 18, X. The most frequently found was the centric minute structure. To date, this group of seven patients constitutes the largest clinical and cytogenetically finely described study of cases with pigmentary mosaicism associated with sSMCs. Undoubtedly, analysis of the two skin types is a fundamental part of our study, as numerical differences may occur in the cell lines found in each skin type. The knowledge generated in this study will help delineate a very heterogeneous entity more accurately, and in the future, analyzing more patients with PM will likely establish a more definite association with the presence of this genetic alteration.

Book Review: Small Supernumerary Marker Chromosomes. Basics

This review provides a critical assessment of the content and structure of the recently published book by Dr. Thomas Liehr, 'Small Supernumerary Marker Chromosomes: Basics.'

A case report of Pallister-Killian syndrome with an unusual mosaic supernumerary marker chromosome 12 with interstitial 12p13.1-p12.1 duplication.

Pallister-Killian syndrome (PKS) is a rare inherited disease with multiple congenital anomalies, profound intellectual disability, and the presence in the karyotype of sSMC - i(12)(p10). The frequency of PKS may be underestimated due to problems with cytogenetic diagnosis caused by tissue-specific mosaicism and usually a low percentage of peripheral blood cells containing sSMC. Such tissue-specific mosaicism also complicates a detailed analysis of the sSMC, which, along with the assessment of mosaicism in different tissues, is an important part of cytogenetic diagnosis in PKS. Unfortunately, a full-fledged diagnosis in PKS is either practically impossible or complicated. On the one hand, this is due to problems with the biopsy of various tissues (skin biopsy with fibroblast culture is most often used in practice); on the other - a low percentage of dividing peripheral blood cells containing sSMC, which often significantly complicates the analysis of its composition and organization. In the present study, a detailed analysis of sSMC was carried out in a patient with a characteristic clinical picture of PKS. A relatively high percentage of peripheral blood cells with sSMC (50%) made it possible to perform a detailed molecular cytogenetic analysis of de novo sSMC using chromosomal in situ suppression hybridization (CISS-hybridization), multicolor FISH (mFISH), multicolor chromosome banding (MCB), array CGH (aCGH), and quantitative real-time PCR (qPCR), and short tandem repeat (STR) - analysis. As a result, it was found that the sSMC is not a typical PKS derivative of chromosome 12. In contrast to the classical i(12)(p10) for PKS, the patient's cells contained an acrocentric chromosome consisting of 12p material. Clusters of telomeric repeats were found at the both ends of the sSMC. Furthemore, the results of aCGH and qPCR indicate the presence of interstitial 8.9Mb duplication at 12p13.1-p12.1 within the sSMC, which leads to different representations of DNA from different segments of 12p within cells containing sSMC. The obtained data raise the question of the instability of the sSMC and, as a consequence, the possible presence of additional rearrangements, which, in traditional cytogenetic analysis of patients with PKS, are usually described as i(12)(p10).

Mosaic Potocki-Lupski Syndrome Due to a Supernumerary Marker Chromosome Containing &lt;i&gt;RAI1&lt;/i&gt;

Potocki-Lupski syndrome&lt;strong&gt; &lt;/strong&gt;(PTLS) is a recurrent microduplication syndrome characterized by developmental delay, behavioral abnormalities, mildly dysmorphic facial features, hypotonia, and sleep disorders. We report here a 3-year-old girl diagnosed with mosaic PTLS harboring a supernumerary marker chromosome containing the &lt;em&gt;RAI1&lt;/em&gt; (retinoic acid induced 1) gene. Cytogenetic testing, including chromosomal microarray, karyotype, and FISH analysis, identified a ring chromosome containing portions of chromosomes 14 and 17 in 85% of cells. Clinical features of this individual included atypical facies with frontal bossing, bitemporal narrowing, prominent cupped ears, and mild speech delay. Presented here is a novel case of PTLS associated with mosaic gains of chromosomes 14 and 17. As small supernumerary marker chromosomes (sSMCs) involving non-acrocentric chromosomes are rare, this case contributes to our understanding of phenotypic spectrum associated with sSMC(17).

Investigating Cytogenetic Profiles in Couples Experiencing Recurrent Implantation Failure Post&lt;i&gt; in vitro&lt;/i&gt; Fertilization

This study evaluates how chromosomal factors affect assisted reproduction techniques (ART) challenges among infertile couples, impacting their chances of conception. Chromosomal abnormalities, a leading cause of pregnancy failure and miscarriages, were investigated in a four-year retrospective study involving 100 patients with a history of infertility and unsuccessful IVF treatment. Among these cases, nine (9%) displayed aberrant chromosomal patterns, including balanced translocations (5%), sex chromosome deletions (3%), and one case of a small supernumerary marker chromosome (sSMC) (1%). The results of the present study highlight the importance of integrating comprehensive cytogenetic analysis as a routine diagnostic tool for individuals dealing with infertility, particularly before assisted reproduction techniques, to avert recurrent implantation failure and to enhance their chances of success.

Small supernumerary marker chromosomes in prenatal diagnosis-molecular characterization and clinical outcomes.

Introduction: Small supernumerary marker chromosomes (sSMCs) are infrequent findings in prenatal diagnostics, however they pose a great challenge for prenatal genetic counseling. Methods: We report prenatal 12 sSMC cases detected in a single center during 10years period, their molecular characterization by fluorescence in situ hybridization (FISH) or chromosomal microarray (CMA). Those cases were found among 9620 prenatal diagnostic analyzes by GTG-banding technique. In selected cases, additional UPD testing was also done. Results: Incidence of sSMCs in our study was 0.12%. sSMC characterization was done by FISH in 9 cases, in the remainder of three CMA was employed. The most common sSMC shape was centric minute, followed by inverted duplication and one case with ring conformation. sSMCs originating from acrocentric chromosomes (chromosomes 14, 21 and 22), sex chromosomes (X, Y) and non-acrocentric autosomal chromosomes (chromosome 4 and 18) were confirmed in 3 cases each; no result could be obtained in 3 further cases. Discussion: No anomalies were detected by prenatal ultrasound in any of the cases. In 58% of the cases, outcome was reported as normal at birth, while anomalies at birth were described in one case. Only two patients opted for pregnancy termination. Preterm labor occurred in case of twin pregnancy resulting in stillbirth and early neonatal death of twins. Overall, our study highlights the importance of a sSMC characterization by molecular cytogenomic methods in order to make appropriate genotype-phenotype correlations and ensure adequate genetic counseling.

Молекулярно-цитогенетическая характеристика малых сверхчисленных маркерных хромосом 15 и 22 у асимптоматических носителей

Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be identified unambiguously by standard cytogenetic methods. A comprehensive approach involving the use of molecular cytogenetic methods is required for the more thorough morphological assessment of such chromosomes, as well as for the development of strategy for genetic counseling of the patients being the sSMC carriers. It is widely accepted that the development of abnormal phenotype by the patients having sSMC in their karyotype is associated with the presence of euchromatic region material in the marker chromosome. Therefore, it results from the presence of relatively large DNA copy number variations (CNVs) in the form of duplication, triplication, and more increased copy numbers; which are localized in the pericentromeric region of the appropriate chromosome. Pericentromeric CNVs can be involved in the chromosome imbalance in asymptomatic carriers of sSMC as well, however, the boundaries of such imbalance have not been clearly identified. The study was aimed to acquire additional information about the genomic topology of the DNA regions insensitive to the genes copy number increase. FISH analysis with commercial and homemade DNA probes was performed in 18 carriers of sSMC 15 and 22 having no clinically significant phenotypic abnormalities. The molecular cytogenetic testing showed that pericentromeric euchromatic regions sized 1.2 Mb and 714 kb, respectively, were found in 33% of cases (6 out of 18). We assume that these regions comprise no potentially dosage-sensitive genes.

Small supernumerary marker chromosomes derived from human chromosome 11.

Introduction: With only 39 reported cases in the literature, carriers of a small supernumerary marker chromosome (sSMC) derived from chromosome 11 represent an extremely rare cytogenomic condition. Methods: Herein, we present a review of reported sSMC(11), add 18 previously unpublished cases, and closely review eight cases classified as 'centromere-near partial trisomy 11' and a further four suited cases from DECIPHER. Results and discussion: Based on these data, we deduced the borders of the pericentric regions associated with clinical symptoms into a range of 2.63 and 0.96Mb for chromosome 11 short (p) and long (q) arms, respectively. In addition, the minimal pericentric region of chromosome 11 without triplo-sensitive genes was narrowed to positions 47.68 and 60.52Mb (GRCh37). Furthermore, there are apparent differences in the presentation of signs and symptoms in carriers of larger sSMCs derived from chromosome 11 when the partial trisomy is derived from different chromosome arms. However, the number of informative sSMC(11) cases remains low, with overlapping presentation between p- and q-arm-imbalances. In addition, uniparental disomy (UPD) of 'normal' chromosome 11 needs to be considered in the evaluation of sSMC(11) carriers, as imprinting may be an influencing factor, although no such cases have been reported. Comprehensively, prenatal sSMC(11) cases remain a diagnostic and prognostic challenge.

Cat eye syndrome: Clinical, cytogenetics and familial findings in a large cohort of 43 patients highlighting the importance of congenital heart disease and inherited cases.

Cat Eye Syndrome (CES) is a rare genetic disease caused by the presence of a small supernumerary marker chromosome derived from chromosome 22, which results in a partial tetrasomy of 22p-22q11.21. CES is classically defined by association of iris coloboma, anal atresia, and preauricular tags or pits, with high clinical and genetic heterogeneity. We conducted an international retrospective study of patients carrying genomic gain in the 22q11.21 chromosomal region upstream from LCR22-A identified using FISH, MLPA, and/or array-CGH. We report a cohort of 43 CES cases. We highlight that the clinical triad represents no more than 50% of cases. However, only 16% of CES patients presented with the three signs of the triad and 9% not present any of these three signs. We also highlight the importance of other impairments: cardiac anomalies are one of the major signs of CES (51% of cases), and high frequency of intellectual disability (47%). Ocular motility defects (45%), abdominal malformations (44%), ophthalmologic malformations (35%), and genitourinary tract defects (32%) are other frequent clinical features. We observed that sSMC is the most frequent chromosomal anomaly (91%) and we highlight the high prevalence of mosaic cases (40%) and the unexpectedly high prevalence of parental transmission of sSMC (23%). Most often, the transmitting parent has mild or absent features and carries the mosaic marker at a very low rate (<10%). These data allow us to better delineate the clinical phenotype associated with CES, which must be taken into account in the cytogenetic testing for this syndrome. These findings draw attention to the need for genetic counseling and the risk of recurrence.

Genetic analysis of a Chinese pedigree affected with overgrowth syndrome due to a small supernumerary marker chromosome

To carry out genetic analysis for a Chinese pedigree affected with intellectual disability and overgrowth due to a supernumerary marker chromosome (sSMC). A pedigree which had presented at Jiaxing Maternity and Child Health Care Hospital on August 31, 2021 was selected as the study subject, for which chromosomal karyotyping, single nucleotide polymorphism-based microarray (SNP-array), and fluorescence in situ hybridization (FISH) were carried out in combination. SNP-array analysis showed that the proband and his sister had both harbored a 16.1 Mb duplication which encompassed the critical region of 15q26 overgrowth syndrome. FISH confirmed that the proband was 47,XX,+neo(15)(qter→q25.3:)mat, her mother was 47,XX,del(15)(q25.3:),+neo(15)(qter→q25.3:), whilst her father was normal. Application of multiple genetic techniques has facilitated delineation of the origin of sSMC and reliable genetic counseling for this pedigree.

Fetal mosaicism, should conventional karyotype always be performed?

The application of classical cytogenetic and DNA-based molecular techniques to detect cell lineages of mosaicism derived from cultured or noncultured fetal cells may result in discordant results. This retrospective study aimed to assess the inconsistent diagnostic outcomes, technical availability, and limitations of chromosomal microarray analysis (CMA) and karyotyping for mosaicism. A total of 75 fetuses diagnosed with mosaicism by karyotype analysis or CMA were selected, and the results from both the methods were compared and further analyzed. A total of 42 (56%, 42/75) CMA results were consistent with karyotypes, consisting of 22 cases of mosaic sex chromosomal abnormalities, 8 routine autosomal aneuploidy cases, 8 other autosome aneuploidy cases, 3 large cryptic genomic rearrangements, and 1 small supernumerary marker chromosome. Discrepancy between karyotype analysis and CMA was observed in 33 (44%, 33/75) mosaicisms involving 15 sex chromosomal abnormalities, 1 routine autosomal aneuploidies, 5 other autosome aneuploidy cases, 8 large cryptic genomic rearrangements, and 4 small supernumerary marker chromosomes. Considering the disparities between methods as well as the cell populations analyzed, both CMA and karyotype analysis have their own advantages and disadvantages. Therefore, CMA should ideally be used in combination with karyotyping to detect more cases of mosaicism than using either test alone.

Molecular and cytogenetic analysis of small supernumerary marker chromosomes in prenatal diagnosis

BackgroundSmall supernumerary marker chromosome (sSMC) is a structurally abnormal chromosome of unknown origin by conventional cytogenetics. The understanding of clinical significance of sSMC is still limited in prenatal diagnosis. The presence of sSMC poses a challenge for genetic counselling.MethodsWe obtained the clinical information of 25 cases with sSMC. The fetal samples were subjected to multiple molecular and cytogenetic approaches including karyotype analysis, chromosomal microarray analysis, bacterial artificial chromosomes-on-beads assay, and fluorescence in situ hybridization.ResultsSeven sSMCs were found to be r(X), and five of the cases terminated the pregnancy. Three markers were idic(15), and one of the cases was normal at birth. Two markers were i(12p), and both cases terminated the pregnancy. Other markers were r(Y) (outcome: normal at birth), i(18p) (outcome: stillbirth), der(15) (outcome: terminated), del(9) (outcome: terminated), dup(13) (outcome: follow-up loss), and derived from chromosome 21 (outcome: stillbirth). Seven markers were of unknown origin because not all methods were applied to them.ConclusionApplying multiple molecular and cytogenetic approaches could identify the origin and genetic content of sSMC to assist the genetic counselling in prenatal diagnosis.

Cytogenetic studies in reproductive function disorders: a retrospective analysis

Aim. Fertility disorders are one of the most common problems of reproductive medicine. Chromosomal abnormalities play a crucial role in reproductive failure. The main purpose of our study was to determine the types and frequency of chromosomal aberrations in couples with history of infertility. Methods. Karyotyping was performed in 652 couples with reproductive failure between 2004 and 2022, including 203 couples with primary infertility (PI), 240 couples with recurrent pregnancy loss (RPL) and 209 – with sporadic pregnancy loss (SPL). Results. Numerical and structural karyotype abnormalities were detected in 37 (2.84 %) of 1304 individuals with infertility, most frequently in group with PI – 3.4 % and RPL – 3.3 %. Chromosomal abnormalities were detected in 3.1 % woman and 2.6 % men. The most common cytogenetic abnormalities (26 cases of 37; 2 %) are translocations, reciprocal – 18 cases (1.4 %) and Robertsonian – 8 cases (0.6 %). Numerical and structural gonosomal abnormalities were detected in 9 individuals (0.7 %), supernumerary marker chromosome – in 2 (0.14 %). Conclusions. Karyotype abnormalities are most common in individuals with PI and RPL and a occur with the same frequency among women and men. Numerical gonosomal abnormalities were detected only as mosaic form.

Characteristics and mechanisms of mosaicism in prenatal diagnosis cases by application of SNP array

BackgroundWith the application of chromosome microarray, next-generation sequencing and other highly sensitive genetic techniques in disease diagnosis, the detection of mosaicism has become increasingly prevalent. This study involved a retrospective analysis of SNP array testing on 4512 prenatal diagnosis samples, wherein the characterization of mosaicism was explored and insights were gained into the underlying mechanisms thereof.ResultsUsing SNP array, a total of 44 cases of mosaicism were identified among 4512 prenatal diagnostic cases; resulting in a detection rate of approximately 1.0%. The prevalence of mosaicism was 4.1% for chorionic villus sample, 0.4% for amniotic fluid, and 1.3% for umbilical cord blood. Of these cases, 29 were mosaic aneuploidy and 15 were mosaic segmental duplication/deletion. Three cases of mosaic trisomy 16 and three cases of mosaic trisomy 22 were diagnosed in the CVS samples, while four cases of mosaic trisomy 21 were detected in amniotic fluid and umbilical cord blood samples. The distribution pattern of mosaicism suggested trisomy rescue as the underlying mechanism. Structurally rearranged chromosomes were observed, including three cases with supernumerary marker chromosomes, three cases with dicentric chromosomes, and one case with a ring chromosome. All mosaic segmental duplication/deletion cases were the result of mitotic non-disjunction, with the exception of one case involving mosaic11q segmental duplication.ConclusionImproved utilization of SNP arrays enables the characterization of mosaicism and facilitates the estimation of disease mechanisms and recurrence.

Role of comprehensive cytogenomic investigation in successful reproductive outcome of parental small neocentromeric supernumerary ring chromosome: A case report

Small supernumerary marker chromosomes (sSMC) can form small supernumerary ring chromosomes (sSRC). Loss of parentally inherited sSRC containing vital gene content may cause an "unbalanced" karyotype and fetal microdeletion syndromes. Rarely, sSRC with neocentromere can be inherited, leading to a "balanced" karyotype, which can be diagnosed with preimplantation genetic testing.

Supernumerary Marker Chromosome Identified in Asian Elephant (Elephas maximus).

We identified a small, supernumerary marker chromosome (sSMC) in two phenotypically normal Asian elephants (Elephas maximus): a female (2n = 57,XX,+mar) and her male offspring (2n = 57,XY,+mar). sSMCs are defined as structurally abnormal chromosomes that cannot be identified by conventional banding analysis since they are usually small and often lack distinct banding patterns. Although current molecular techniques can reveal their origin, the mechanism of their formation is not yet fully understood. We determined the origin of the marker using a suite of conventional and molecular cytogenetic approaches that included (a) G- and C-banding, (b) AgNOR staining, (c) preparation of a DNA clone using laser microdissection of the marker chromosome, (d) FISH with commercially available human painting and telomeric probes, and (e) FISH with centromeric DNA derived from the centromeric regions of a marker-free Asian elephant. Moreover, we present new information on the location and number of NORs in Asian and savanna elephants. We show that the metacentric marker was composed of heterochromatin with NORs at the terminal ends, originating most likely from the heterochromatic region of chromosome 27. In this context, we discuss the possible mechanism of marker formation. We also discuss the similarities between sSMCs and B chromosomes and whether the marker chromosome presented here could evolve into a B chromosome in the future.

Molecular delineation of de novo small supernumerary marker chromosomes in prenatal diagnosis, a retrospective study

ObjectivesTo define the genotype-phenotype correlation of small supernumerary marker chromosomes (sSMCs) and conduct precise genetic counseling, we retrospectively searched and reviewed de novo sSMCs cases detected during prenatal diagnosis at The First Affiliated Hospital of Zhengzhou University. Materials and methodsChromosome karyotypes of 20,314 cases of amniotic fluid from pregnant women were performed. For 16 samples with de novo sSMCs, 10 were subjected to single-nucleotide polymorphism (SNP) array or low-coverage massively parallel copy number variation sequencing (CNV-seq) analysis. ResultsAmong the 10 sSMCs cases, two sSMCs derived from chromosome 9, and three sSMCs derived from chromosomes 12, 18 and 22. The remaining 5 cases were not identified by SNP array or CNV-seq because they lacked euchromatin or had a low proportion of mosaicism. Four of them with a karyotype of 47,XN,+mar presented normal molecular cytogenetic results (seq[hg19] 46,XN), and the remaining patient with a karyotype of 46,XN,+mar presented with Turner syndrome (seq[hg19] 45,X). Five sSMCs samples were mosaics of all 16 cases. ConclusionConsidering the variable origins of sSMCs, further genetic testing of sSMCs should be performed by SNP array or CNV-seq. Detailed molecular characterization would allow precise genetic counseling for prenatal diagnosis.

Мейотическая сегрегация и межхромосомный эффект гетерохроматиновых малых сверхчисленных маркерных хромосом

Введение. Малые сверхчисленные маркерные хромосомы (мСМХ), состоящие из гетерохроматиновых районов, могут быть обнаружены у индивидуумов без видимых аномалий фенотипа. Их наличие в кариотипе иногда приводит к репродуктивным проблемам, связанным с риском возникновения ошибок мейоза вследствие нарушения межхромосомного синапсиса и процесса расхождения гомологичных хромосом. Цель: изучение мейотической сегрегации и оценка частоты формирования гамет с анеуплоидией у мужчин с кариотипом 47,XY,+mar без клинически значимых аномалий фенотипа. Материалы и методы: флуоресцентная in situ гибридизация (FISH) на препаратах из эякулята семи мужчин, асимптоматических носителей мСМХ. Результаты: у всех носителей мСМХ частота сперматозоидов, содержащих маркерную хромосому, не превышала 28% и в среднем составляла 15,04±9,4 (±SD). Доля анеуплоидных сперматозоидов не превышала 3,1% и в среднем составляла 1,9±1,1 что сопоставимо с частотой анеуплоидии в гаметах индивидуумов с различными показателями спермы и нормальным кариотипом, которая не превышает 5,9% и в среднем составляет 2,2±1,8. Выводы: в мейозе носителей гетерохроматиновых мСМХ гаметы преимущественно формируются без маркерной хромосомы. Показано, что присутствие мСМХ в клетках эякулята не оказывает существенного влияния на мейотическую сегрегацию других хромосом, т.е. межхромосомный эффект отсутствует. Introduction. Small supernumerary marker chromosomes (sSMCs) consisting of heterochromatin regions can be found in individuals without visible phenotypic abnormalities. Their presence in the karyotype sometimes leads to reproductive problems associated with the risk of meiosis errors due to interchromosomal synapses and the process of non-disjunction of homologous chromosomes. Aim: to investigate meiotic segregation and evaluate the frequency of gamete formation with aneuploidy in males with karyotype 47,XY,+mar without clinically significant phenotypic abnormalities. Materials and Methods: fluorescence in situ hybridization (FISH) on fixed sperm preparations in 7 male patients-asymptomatic carriers of sSMC. Results. In all sSMC carriers, the frequency of spermatozoa containing the marker chromosome did not exceed 30% and averaged 15.04±9.4 (±SD). The proportion of aneuploid spermatozoa did not exceed 3.1% and, on average, was 1.9%±1.1, which does not differ from the frequency of aneuploidy in gametes in individuals with normal karyotype (does not exceed 5.9% and, on average, is 2.2±1.8). Conclusions. In carriers of heterochromatinous sSMC gametes in meiosis are predominantly formed without a marker chromosome. It has been shown that the presence of a high proportion of sSMC in the ejaculate cells does not significantly affect the meiotic segregation of other chromosomes, i.e., there is no interchromosomal effect.