scholarly journals Ring chromosome 3 instability at mitosis

2019 ◽  
pp. 40-45
Author(s):  
Н.В. Шилова ◽  
М.Е. Миньженкова ◽  
Ж.Г. Маркова ◽  
А.А. Тарлычева ◽  
Д.А. Юрченко
Keyword(s):  
Ring Chromosome ◽  
Postnatal Growth ◽  
Chromosome 3 ◽  
Fish Analysis ◽  
Developmental Abnormalities ◽  
Dysmorphic Features ◽  
Severe Intellectual Disability ◽  
Ring Chromosomes ◽  
Mitotic Instability ◽  
Variable Phenotype

Актуальность. Кольцевая хромосома 3 - редкая хромосомная аномалия, характеризующаяся выраженной вариабельностью фенотипических отклонений. Наиболее характерными проявлениями присутствия в кариотипе кольцевой хромосомы 3 являются пре- и постнатальная задержка роста, задержка психомоторного развития, микроцефалия и другие аномалии развития. Кольцевая структура может приводить к нарушению нормального расхождения хромосом при клеточном делении и вызывает митотическую нестабильность, приводящую к динамическому мозаицизму. В данном сообщении представлен случай митотической нестабильности кольцевой хромосомы 3 у ребенка с множественными пороками и аномалиями развития, демонстрирующий влияние вторичного хромосомного дисбаланса на степень выраженности фенотипических аномалий. Цель: исследование митотической нестабильности кольцевой хромосомы 3. Методы: FISH с ДНК-зондами на хромосому 3. Результаты. При стандартном цитогенетическом исследовании определен кариотип 46,XX,r(3)(p26q29). При FISH-анализе обнаружено наличие нескольких клонов клеток, содержащих различные варианты аномальных по структуре производных кольцевой хромосомы 3. Выводы. Присутствие кольцевых хромосом в геноме является причиной митотической нестабильности, что приводит к формированию соматического динамического мозаицизма. Соматический динамический мозаицизм, вследствие которого образуются клоны клеток с различным хромосомным дисбалансом, вносит существенный вклад в формирование аномального фенотипа. Ring chromosome 3 is a rare chromosomal abnormality with a highly variable phenotype principally characterized by pre- and postnatal growth retardation, developmental delay, mild to severe intellectual disability, microcephaly and mild dysmorphic features. The presence of a ring chromosome causes mitotic instability and often results in dynamic mosaicism with cells showing chromosomal or segmental aneuploidies and leading to various phenotypic consequences. We present a case of mitotic instability of ring chromosome 3 in a child with multiple malformations and developmental abnormalities. Aim: The investigation of ring chromosome 3 instability at mitosis. Methods: FISH with DNA probe on chromosome 3. Results: The karyotype of a child - 46,XX,r(3)(p26q29). FISH analysis revealed a mosaic clones derived from ring chromosome 3. Conclusions: The ring chromosomes are unstable at mitosis and lead to the formation of somatic dynamic mosaicism. Mitotic instability of ring chromosome 3 demonstrates the influence of secondary genetic imbalance on severity of symptoms in our patient.

scholarly journals Ring Chromosome 20 Associated with Refractory Epilepsy: A Case Report

2012 ◽  
Vol 2 (3) ◽  
pp. 141-144
Author(s):  
A Radha Rama Devi ◽  
Usha R Dutta
Keyword(s):  
Behavioral Problems ◽  
Refractory Epilepsy ◽  
Ring Chromosome ◽  
Epileptic Seizures ◽  
Dysmorphic Features ◽  
Mild Developmental Delay ◽  
Chromosome 20 ◽  
First Case ◽  
South Indian ◽  
Ring Chromosomes

Ring chromosome 20 is a rare chromosomal abnormality characterized mainly by refractory epileptic seizures, cognitive and behavioral problems, and absence of definite dysmorphic features. We report a 5-year-old boy with refractory epilepsy and minimal dysmorphic features who first presented with mild developmental delay at 11 months of age. The karyotype of the child was 46,XY,r(20)(p13q13.3). Till date there are 69 cases of ring chromosome 20 reported in the literature, including mosaics and supernumerary ring chromosomes. To our knowledge, this is the first case of ring chromosome 20 with refractory epilepsy reported from the south Indian population.DOI: http://dx.doi.org/10.3126/ajms.v2i3.5607Asian Journal of Medical Sciences 2 (2011) 141-144

Prenatal diagnosis of ring chromosome 13: a rare chromosomal aberration

2018 ◽  
Vol 7 (2) ◽  
Author(s):  
Haruka Goto ◽  
Yasuyuki Fujita ◽  
Yuka Sato ◽  
Saki Kido ◽  
Masanobu Ogawa ◽  
...  
Keyword(s):  
Chromosomal Aberration ◽  
Good Condition ◽  
Ring Chromosome ◽  
Japanese Woman ◽  
Trisomy 13 ◽  
Fish Analysis ◽  
Chromosome 13 ◽  
Ring Chromosomes ◽  
Banding Analysis ◽  
Female Baby

Abstract We report the case of a 24-year-old Japanese woman, gravida 2, para 1, who became pregnant spontaneously. At 24 weeks of gestation, her fetus was found to have various abnormalities, including holoprosencephaly, congenital heart disease and severe fetal growth restriction, and she was referred to our hospital. From these findings, the fetus was suspected of having a chromosomal aberration, in particular, trisomy 13, and after genetic counseling, amniocentesis for chromosomal analysis was performed. Although the results of fluorescent in situ hybridization (FISH) analysis showed no numeric abnormalities, G-banding analysis revealed a ring chromosome 13; 46, XX, r (13) (p13q32). At 41 weeks of gestation, she delivered a female baby weighing 2240 g with good condition. The respiratory status of the neonate was stable, and she was discharged 30 days after birth. Ring chromosomes are rare chromosomal aberrations, and obstetricians should recognize that ring chromosomes cannot be detected solely by FISH analysis and require G-banding analysis and that information on the ring breakpoint is needed to counsel the parents regarding the fetal and neonatal prognosis.

35-Year Follow-Up of a Case of Ring Chromosome 2: Array-CGH Analysis and Literature Review of the Ring Syndrome

2015 ◽  
Vol 145 (1) ◽  
pp. 6-13
Author(s):  
Catherine Sarri ◽  
Sofia Douzgou ◽  
Haris Kontos ◽  
Katherine Anagnostopoulou ◽  
Zeynep Tümer ◽  
...  
Keyword(s):  
Array Cgh ◽  
Growth Failure ◽  
Ring Chromosome ◽  
Fish Analysis ◽  
Chromosome 2 ◽  
Common Pattern ◽  
Ring Chromosomes ◽  
Minor Anomalies ◽  
General Ring

Côté et al. [1981] suggested that ring chromosomes with or without deletions share a common pattern of phenotypic anomalies, regardless of which chromosome is involved. The phenotype of this ‘general ring syndrome' consists of growth failure without malformations, few or no minor anomalies, and mild to moderate mental retardation. We reconsidered the ring chromosome 2 case previously published by Côté et al. [1981], and we characterized it by array CGH, polymorphic markers as well as subtelomere MLPA and FISH analysis. A terminal deletion (q37.3qter) of maternal origin of the long arm of the ring chromosome 2 was detected and confirmed by all the above-mentioned methods. Ring chromosome 2 cases are exceedingly rare. Only 18 cases, including the present one, have been published so far, and our patient is the longest reported survivor, with a 35-year follow-up, and the third case characterized by array-CGH analysis.

scholarly journals 46,XY,r(8)/45,XY,−8 Mosaicism as a Possible Mechanism of the Imprinted Birk-Barel Syndrome: A Case Study

Genes ◽  
2020 ◽  
Vol 11 (12) ◽  
pp. 1473
Author(s):  
Anna A. Kashevarova ◽  
Tatyana V. Nikitina ◽  
Larisa I. Mikhailik ◽  
Elena O. Belyaeva ◽  
Stanislav A. Vasilyev ◽  
...  
Keyword(s):  
De Novo ◽  
Snp Array ◽  
Ring Chromosome ◽  
Chromosome 8 ◽  
Fish Analysis ◽  
Feeding Problems ◽  
Maternal Chromosome ◽  
Imprinting Disorder ◽  
Ring Chromosomes ◽  
Normal Copy Number

Ring chromosome 8 (r(8)) is one of the least frequent ring chromosomes. Usually, maternal chromosome 8 forms a ring, which can be lost from cells due to mitotic instability. The 8q24 region contains the imprinted KCNK9 gene, which is expressed from the maternal allele. Heterozygous KCNK9 mutations are associated with the imprinting disorder Birk-Barel syndrome. Here, we report a 2.5-year-old boy with developmental delay, microcephaly, dysmorphic features, diffuse muscle hypotonia, feeding problems, motor alalia and noncoarse neurogenic type of disturbance of muscle electrogenesis, partially overlapping with Birk-Barel syndrome phenotype. Cytogenetic analysis of lymphocytes revealed his karyotype to be 46,XY,r(8)(p23q24.3)[27]/45,XY,−8[3]. A de novo 7.9 Mb terminal 8p23.3p23.1 deletion, a 27.1 Mb 8p23.1p11.22 duplication, and a 4.4 Mb intact segment with a normal copy number located between them, as well as a 154-kb maternal LINGO2 gene deletion (9p21.2) with unknown clinical significance were identified by aCGH + SNP array. These aberrations were confirmed by real-time PCR. According to FISH analysis, the 8p23.1-p11.22 duplication was inverted. The ring chromosome originated from maternal chromosome 8. Targeted massive parallel sequencing did not reveal the KCNK9 mutations associated with Birk-Barel syndrome. Our data allow to assume that autosomal monosomy with inactive allele of imprinted gene arising from the loss of a ring chromosome in some somatic cells may be an etiological mechanism of mosaic imprinting disorders, presumably with less severe phenotype.

scholarly journals MEIOTIC AND MITOTIC BEHAVIOR OF DICENTRIC CHROMOSOMES IN SACCHAROMYCES CEREVISIAE

Genetics ◽  
1984 ◽  
Vol 106 (2) ◽  
pp. 185-205
Author(s):  
James E Haber ◽  
Patricia C Thorburn ◽  
David Rogers
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Recombinant Dna ◽  
Ring Chromosome ◽  
Dicentric Chromosome ◽  
Linear Chromosome ◽  
Dicentric Chromosomes ◽  
Ring Chromosomes ◽  
Mitotic Instability ◽  
Unequal Number ◽  
Chromosome Iii

ABSTRACT Meiotic recombination between a circular and a linear chromosome in Saccharomyces cerevisiae has been investigated. The circle was a haploid-viable derivative of chromosome III constructed by joining regions near the two chromosome ends via a recombinant DNA construction: (HMR/MAT-URA3-pBR322-MAT/HML) and was also deleted for MAL2(which therefore uniquely marks a linear chromosome III). Recombination along chromosome III was measured for eight intervals spanning the entire length of the circular derivative. Only 25% of all tetrads from a ring/rod diploid contained four viable spores. These proved to be cases in which there was either no recombination along chromosome III or in which there were two-strand double crossovers or higher order crossovers that would not produce a dicentric chromosome.—At least half of the tetrads with three viable spores included one Ura+ Mal+ spore that was genetically highly unstable. The Ura+ Mal+ spore colonies gave rise to as many as seven genetically distinct, stable ("healed") derivatives, some of which had lost either URA3 or MAL2. Analysis of markers on chromosome III suggests that dicentric chromosomes frequently do not break during meiosis but are inherited intact into a haploid spore. In mitosis, however, the dicentric chromosome is frequently broken, giving rise to a variety of genetically distinct derivatives. We have also shown that dicentric ring chromosomes exhibit similar behavior: at least half the time they are not broken during meiosis but are broken and healed during mitosis.—The ring/rod diploid can also be used to determine the frequency of sister chromatid exchange (SCE) along an entire yeast ring chromosome. We estimate that an unequal number of SCE events occurs in approximately 15% of all cells undergoing meiosis. In contrast, the mitotic instability (and presumably SCE events) of a ring chromosome is low, occurring at a rate of about 1.2 x 10-3 per cell division.

Modeling of dynamic mosaicism on ring chromosomes in human fibroblasts and IPSCS

2020 ◽  
pp. 12-13
Author(s):  
Т.В. Никитина ◽  
А.А. Кашеварова ◽  
М.М. Гридина ◽  
А.А. Хабарова ◽  
А.Г. Мензоров ◽  
...  
Keyword(s):  
Genetic Structure ◽  
Human Fibroblasts ◽  
Cellular Heterogeneity ◽  
Mitotic Stability ◽  
Factors Affecting ◽  
Ring Chromosomes ◽  
Cell Clones ◽  
Mitotic Instability ◽  
Mitotic Behavior

Митотическая нестабильность кольцевых хромосом может приводить к появлению клеточных клонов с различной генетической структурой. В качестве модели нестабильности кольцевых хромосом в митозе мы использовали фибробласты от пациентов с r(8), r(13), r(18) и r(22) и полученные из них индуцированные плюрипотентные стволовые клетки (ИПСК). Линии ИПСК с r(22) имели относительно стабильный кариотип на протяжении десятков (до 60) пассажей и сохраняли неизменную структуру кольцевой хромосомы. Кариотип линий ИПСК с r(8) и r(18) на ранних пассажах стабильный, планируется его изучение на поздних пассажах. Наибольшее разнообразие кариотипа выявлено в линиях ИПСК с r(13), в которых наблюдали различные перестройки и выраженную клеточную гетерогенность. Определение факторов, влияющих на митотическую стабильность кольцевых хромосом, может иметь значение для консультирования пациентов. Mitotic instability of ring chromosomes can lead to the appearance of cell clones with different genetic structure. IPSCs from fibroblasts of patients with r(8), r(13), r(18), and r(22) were used as a model of ring chromosomes mitotic behavior. Karyotypes of iPSC lines with r(8) and r(18) have so far been evaluated only in the early passages, lines with r(22) have maintained a relatively stable karyotype up to 60 passages. The occurrence of rearrangements and cellular heterogeneity was found characteristic for r(13) iPSCs. The determination of factors affecting the ring chromosomes mitotic stability would be beneficial for the patient’s prognosis.

scholarly journals Distal Partial Trisomy 15q26 and Partial Monosomy 16p13.3 in a 36-Year-Old Male with Clinical Features of Both Chromosomal Abnormalities

2015 ◽  
Vol 145 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Devin M. Cox ◽  
Merlin G. Butler
Keyword(s):  
Intellectual Disability ◽  
Chromosomal Abnormalities ◽  
Receptor Gene ◽  
Partial Trisomy ◽  
Chromosome Translocation ◽  
Fish Analysis ◽  
Partial Monosomy ◽  
Chronic Anemia ◽  
Dysmorphic Features ◽  
History Of

We report a 36-year-old Caucasian male identified with distal partial trisomy 15q and partial monosomy 16p from an unbalanced chromosome translocation detected by microarray and FISH analysis. He had a history of developmental delay and intellectual disability, chronic anemia, tall and slender stature, thoracic scoliosis and lumbar lordosis, and dysmorphic features. The distal partial trisomy 15q included the insulin-like growth factor 1 receptor gene involved with growth, while genes in the distal partial monosomy 16p region are involved with alpha hemoglobin production, intellectual disability, dysmorphic features, and acromegaly. The chromosome derivative found in our patient contains genes known to play a role in his phenotype.

The Heterogeneous Distribution of Monosomy 3 in Uveal Melanomas: Implications for Prognostication Based on Fine-Needle Aspiration Biopsies

2007 ◽  
Vol 131 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Willem Maat ◽  
Ekaterina S. Jordanova ◽  
Shama L. van Zelderen-Bhola ◽  
Ed R. Barthen ◽  
Hans W. Wessels ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Fine Needle Aspiration ◽  
Fine Needle Aspiration Biopsy ◽  
Needle Aspiration ◽  
Chromosome 3 ◽  
Fish Analysis ◽  
Paraffin Sections ◽  
Heterogeneous Distribution ◽  
Fine Needle ◽  
Monosomy 3

Abstract Context.—The detection of monosomy 3 in uveal melanomas has repeatedly been associated with adverse outcome. Fine-needle aspiration biopsy is being used to detect monosomy 3 in these tumors, based on the assumption that this chromosomal abnormality is distributed homogeneously throughout the tumor. Objective.—To study the distribution of monosomy 3 in primary uveal melanoma by fluorescence in situ hybridization (FISH). Design.—We studied 50 enucleated eyes with uveal melanoma. In all 50 tumors we performed cytogenetic analysis and FISH using a DNA-specific probe for the centromere region of chromosome 3 on cultured tumor cells. In addition, the percentage of tumor cells with monosomy 3 was assessed by FISH on nuclei, isolated from paraffin-embedded tissue and compared to results of FISH on regular histology sections of the paraffin-embedded tissue. Results.—Combining karyotyping and FISH on cultured cells identified monosomy 3 in 19 (38%) of 50 tumors, whereas FISH on nuclei isolated from paraffin-embedded tissue showed 31 (62%) of 50 as having monosomy for chromosome 3. FISH analysis on paraffin sections showed tumor heterogeneity for copy number of chromosome 3 in at least 7 cases. Conclusions.—FISH analysis on paraffin sections shows that heterogeneity of monosomy of chromosome 3 is a frequent phenomenon in uveal melanoma. FISH on nuclei isolated from paraffin-embedded tissue identifies a higher frequency of monosomy 3 than the traditional combination of karyotyping and FISH on cultured uveal melanoma cells. The practice of assigning patients to risk categories based on fine-needle aspiration biopsy samples from primary uveal melanoma may be subject to error based on the heterogeneous distribution of monosomy 3 in these tumors.

scholarly journals Identification of an Identical de Novo SCAMP5 Missense Variant in Four Unrelated Patients With Seizures and Severe Neurodevelopmental Delay

2020 ◽  
Vol 11 ◽  
Author(s):  
Xianru Jiao ◽  
Manuela Morleo ◽  
Vincenzo Nigro ◽  
Annalaura Torella ◽  
Stefano D’Arrigo ◽  
...  
Keyword(s):  
Language Development ◽  
Developmental Disorders ◽  
De Novo ◽  
Brain Mri ◽  
Brain Magnetic Resonance Imaging ◽  
Autism Spectrum ◽  
Neurodevelopmental Delay ◽  
Dysmorphic Features ◽  
Severe Intellectual Disability ◽  
Neurological Exam

Objective: To establish and broaden the phenotypic spectrum of secretory carrier membrane protein (SCAMP5) associated with epilepsy and neurodevelopmental delay.Methods: A Chinese patient was identified at the First Hospital of Peking University, and the three unrelated patients were recruited from two different countries (Italy and United States) through GeneMatcher. SCAMP5 pathogenic variants were identified by whole exome sequencing; clinical data of the patients were retrospectively collected and analyzed.Result: The onset age of seizures was ranged from 6 to 15 months. Patients had different types of seizures, including focal seizures, generalized tonic-clonic seizures and tonic seizure. One patient showed typical autism spectrum disorder (ASD) symptoms. Electroencephalogram (EEG) findings presented as focal or multifocal discharges, sometimes spreading to generalization. Brain magnetic resonance imaging (MRI) abnormalities were present in each patient. Severe intellectual disability and language and motor developmental disorders were found in our patients, with all patients having poor language development and were nonverbal at last follow-up. All but one of the patients could walk independently in childhood, but the ability to walk independently in one patient had deteriorated with age. All patients had abnormal neurological exam findings, mostly signs of extrapyramidal system involvement. Dysmorphic features were found in 2/4 patients, mainly in the face and trunk. All four unrelated patients were found to have the same heterozygous pathogenic SCAMP5 de novo variant (p. Gly180Trp).Conclusion: Epilepsy, severe developmental delay, abnormal neurological exam findings, with or without ASD or variably dysmorphic features and were common in patients with SCAMP5 variant. The onset time and type of seizure varied greatly. The EEG and brain MRI findings were not consistent, but diverse and nonspecific. The motor ability of patients with heterozygous SCAMP5 variant might have a regressive course; language development was more severely affected.

scholarly journals Human Ring Chromosomes – New Insights for their Clinical Significance

2013 ◽  
Vol 16 (1) ◽  
pp. 13-19 ◽  
Author(s):  
R.S. Guilherme ◽  
E Klein ◽  
A.B. Hamid ◽  
S Bhatt ◽  
M Volleth ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Clinical Signs ◽  
Ring Chromosome ◽  
Signs And Symptoms ◽  
Molecular Techniques ◽  
Ring Chromosomes ◽  
Multicolor Banding ◽  
Clinical Signs And Symptoms ◽  
Clinical Problems

Abstract Twenty-nine as yet unreported ring chromosomes were characterized in detail by cytogenetic and molecular techniques. For FISH (fluorescence in situ hybridization) previously published high resolution approaches such as multicolor banding (MCB), subcentromere-specific multi-color-FISH (cenM-FISH) and two to three-color-FISH applying locus-specific probes were used. Overall, ring chromosome derived from chromosomes 4 (one case), 10 (one case), 13 (five cases), 14, (three cases), 18 (two cases), 21 (eight cases), 22 (three cases), X (five cases) and Y (one case) were studied. Eight cases were detected prenatally, eight due developmental delay and dysmorphic signs, and nine in connection with infertility and/or Turner syndrome. In general, this report together with data from the literature, supports the idea that ring chromosome patients fall into two groups: group one with (severe) clinical signs and symptoms due to the ring chromosome and group two with no obvious clinical problems apart from infertility.

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