Complex approach to the study of the Derivative Chromosome 8

2021 ◽  
pp. 41-50
Author(s):  
Д.А. Юрченко ◽  
М.Е. Миньженкова ◽  
Ж.Г. Маркова ◽  
Е.Л. Дадали ◽  
Н.В. Шилова
Keyword(s):  
De Novo ◽  
Cytogenetic Study ◽  
Chromosomal Rearrangements ◽  
Dna Probes ◽  
Chromosome 8 ◽  
Abnormal Chromosome ◽  
Derivative Chromosome ◽  
Chromosomal Imbalance ◽  
Complex Approach ◽  
Mechanisms Of Formation

Введение. Дериватная хромосома (der) - структурно аномальная хромосома, формирование которой может происходить как в результате перестроек с участием двух и более негомологичных хромосом, так и вследствие аберраций внутри одной хромосомы. Дифференциальная диагностика дериватных хромосом очень важна для выяснения происхождения хромосомной аномалии и для определения тактики медико-генетического консультирования с целью оценки повторного риска рождения ребенка с хромосомным дисбалансом. В данной работе представлены семь случаев дериватной хромосомы 8, имеющих различное происхождение и механизмы формирования, а также протокол обследования пациентов с дериватной хромосомой 8 в кариотипе. Цель: изучить структуру и механизмы формирования дериватных хромосом 8. Методы: стандартное цитогенетическое исследование, M-FISH, MCB8, FISH с локус-специфичными субтеломерными ДНК-зондами, FISH с несерийными ДНК-зондами на район р23.1 хромосомы 8. Результаты. В результате проведенного стандартного цитогенетического исследования в кариотипе семи неродственных пробандов была обнаружена дериватная хромосома 8. При использовании цитогенетического и молекулярно-цитогенетического подходов было установлено, что у четырех пациентов дериватная хромосома 8 возникла в результате инвертированной дупликации/делеции 8р, а у трех - несбалансированной транслокации с участием хромосомы 8: der(8)t(8;17), der(8)t(8;12) и der(8)t(7;8). Во всех случаях был определен механизм формирования хромосомных перестроек. Дериватные хромосомы транслокационного происхождения в двух случаях были сформированы de novo, а в одном случае - как результат патологической мейотической сегрегации отцовской реципрокной транслокации. Все дериватные хромосомы с инвертированной дупликацией/делецией 8р были следствием эктопической рекомбинации. Заключение. Представленные результаты демонстрируют целесообразность комплексного лабораторного подхода в изучении структуры и происхождения дериватной хромосомы 8. Характеристика происхождения хромосомного дисбаланса является неотъемлемой частью обследования пациентов со структурно аномальной хромосомой 8 в кариотипе. Background. Derivative chromosome (der) is a structurally abnormal chromosome, the formation of which can occur as a result of rearrangements with the participation of two or more non-homologous chromosomes, or be the result of aberrations within one chromosome. Differential diagnosis of derivative chromosomes is very important for clarifying the origin of the chromosomal abnormality and for determining the tactics of medical genetic counseling in order to assess the repeated risk of chromosomal imbalance. This work presents seven cases of a derivative chromosome with different origins and mechanisms of formation, as well as a protocol for examining patients with derivative chromosome 8 in the karyotype. Aim: to study the structure and mechanisms of formation of the derivative chromosome 8. Methods. GTG-banded chromosomal analysis, M-FISH, MCB8, FISH with subtelomeric DNA probes, FISH with home-made DNA probes for 8p23.1. Results. As a result of a conventional cytogenetic study of seven unrelated probands a derivative chromosome 8 was found. In all cases, the mechanism of the formation of chromosomal rearrangements was determined. Derivative chromosomes of translocation origin were formed de novo in two cases- der(8)t(8;12) and der(8)t(7;8), and in one case -der(8)t(8;17) - as a result of malsegregation of the paternal reciprocal translocation. In the remaining four cases, the derivative chromosomes were identified as an inverted duplication/deletion 8p due to ectopic recombination. Conclusion. The presented results demonstrate the feasibility of an integrated laboratory approach in the diagnosis of derivative chromosome 8. Characterization of the origin of chromosomal imbalance is an integral part of the examination of patients with structurally abnormal chromosome 8 in the karyotype.

scholarly journals A Novel De Novo Chromosomal Insertion, 46 XX, ins(7:13)(p14; q14.2q21.1) is Related to the Embryo Development Arrest Following Assisted Reproductive Technique

2020 ◽  
Author(s):  
Azam Azargoon ◽  
Nahid Azad
Keyword(s):  
Embryo Development ◽  
De Novo ◽  
Chromosomal Rearrangements ◽  
Chromosome 7 ◽  
Infertile Woman ◽  
Normal Male ◽  
Derivative Chromosome ◽  
Assisted Reproductive Technique ◽  
History Of ◽  
Reproductive Technique

Background: Infertility is a problem affecting a large number of couples in the world. One of the causes of infertility can be chromosomal rearrangements such as insertions. In this case report study, the outcome of two intra-cytoplasmic sperm injection (ICSI) cycles of an infertile woman with de novo chromosomal insertion is explained. Case Presentation: A couple with a 10-year history of infertility referred to our infertility clinic. The husband had a daughter in his first previous marriage. The wife had a 7 and a 10 year history of infertility in the first and second marriages, respectively. In the first marriage, she reported a history of 2 failed intra-uterine insemination (IUI) cycles. In the second marriage, she had a history of 1 spontaneous abortion at 12 weeks of pregnancy, 4 failed IUI cycles, and 1 failed ICSI cycle. The couple was subjected to ICSI cycles twice and failed due to embryo development arrest. The couple referred for karyotyping. The husband showed a normal male karyotype. In comparison, the wife revealed an abnormal female karyotype with two rearrangements: chromosome 13 with an interstitial deletion between bands q14.2 and q21.1, and a derivative chromosome 7 containing this segment of chromosome 7 as an insertion onto short arm at the p14 position. Conclusion: To the best of our knowledge, this is the first report of insertion 46 XX, ins(7:13)(p14; q14.2q21.1) which is associated with the embryo development arrest following assisted reproductive technique.

scholarly journals Unusual de novo Partial Trisomy 17p12p11.2 due to Unbalanced Insertion into 5p13.1 in a Severely Affected Boy

2017 ◽  
Vol 06 (03) ◽  
pp. 165-168 ◽  
Author(s):  
Luis Mendez-Rosado ◽  
Araceli Lantigua ◽  
Juan Galarza ◽  
Ahmed Hamid Al-Rikabi ◽  
Monika Ziegler ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Partial Trisomy ◽  
Derivative Chromosome ◽  
Genomic Disorder ◽  
Charcot Marie Tooth Disease ◽  
Dysmorphic Features ◽  
Copy Numbers ◽  
Tooth Disease

AbstractGain of copy numbers can be due to different chromosomal rearrangements such as direct or indirect duplications, translocations, small supernumerary marker chromosomes, or insertions. In a 3-year-old boy with dysmorphic features and developmental delay, chromosome analyses revealed a derivative chromosome 5. Microdissection and reverse fluorescence in situ hybridization identified the in 5p13.1 inserted part as 17p12-p11.2 material. Thus the patient suffered from a rare combination of genomic disorder, that is, Charcot-Marie-Tooth disease type 1A and Potocki-Lupski syndrome. Parental studies indicated that the abnormality was de novo in origin. As the question how this rearrangement arose cannot be answered conclusively, formal genetic counseling is warranted, which includes a discussion regarding the possibility of gonadal mosaicism. In conclusion, this case highlights that chromosome 17p is genetically relatively instable, and thus it can lead to rare chromosomal conditions.

scholarly journals Chromoanagenesis Event Underlies a de novo Pericentric and Multiple Paracentric Inversions in a Single Chromosome Causing Coffin–Siris Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Christopher M. Grochowski ◽  
Ana C. V. Krepischi ◽  
Jesper Eisfeldt ◽  
Haowei Du ◽  
Debora R. Bertola ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Whole Genome Sequencing Data ◽  
Mendelian Disease ◽  
Derivative Chromosome ◽  
Sequencing Data ◽  
End Joining ◽  
Single Chromosome ◽  
Complex Structural ◽  
Non Homologous End Joining

Chromoanagenesis is a descriptive term that encompasses classes of catastrophic mutagenic processes that generate localized and complex chromosome rearrangements in both somatic and germline genomes. Herein, we describe a 5-year-old female presenting with a constellation of clinical features consistent with a clinical diagnosis of Coffin–Siris syndrome 1 (CSS1). Initial G-banded karyotyping detected a 90-Mb pericentric and a 47-Mb paracentric inversion on a single chromosome. Subsequent analysis of short-read whole-genome sequencing data and genomic optical mapping revealed additional inversions, all clustered on chromosome 6, one of them disrupting ARID1B for which haploinsufficiency leads to the CSS1 disease trait (MIM:135900). The aggregate structural variant data show that the resolved, the resolved derivative chromosome architecture presents four de novo inversions, one pericentric and three paracentric, involving six breakpoint junctions in what appears to be a shuffling of genomic material on this chromosome. Each junction was resolved to nucleotide-level resolution with mutational signatures suggestive of non-homologous end joining. The disruption of the gene ARID1B is shown to occur between the fourth and fifth exon of the canonical transcript with subsequent qPCR studies confirming a decrease in ARID1B expression in the patient versus healthy controls. Deciphering the underlying genomic architecture of chromosomal rearrangements and complex structural variants may require multiple technologies and can be critical to elucidating the molecular etiology of a patient’s clinical phenotype or resolving unsolved Mendelian disease cases.

Cerebellotrigeminal Dermal Dysplasia (Gómez-López-Hernández Syndrome)

2018 ◽  
Vol 16 (05) ◽  
pp. 362-368 ◽  
Author(s):  
Federica Sullo ◽  
Agata Polizzi ◽  
Stefano Catanzaro ◽  
Selene Mantegna ◽  
Francesco Lacarrubba ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Number Of Patients ◽  
Wide Range ◽  
Visual Problems ◽  
Neurodevelopmental Abnormalities ◽  
Clinical Triad ◽  
High Degree ◽  
Motor Handicap

Cerebellotrigeminal dermal (CTD) dysplasia is a rare neurocutaneous disorder characterized by a triad of symptoms: bilateral parieto-occipital alopecia, facial anesthesia in the trigeminal area, and rhombencephalosynapsis (RES), confirmed by cranial magnetic resonance imaging. CTD dysplasia is also known as Gómez-López-Hernández syndrome. So far, only 35 cases have been described with varying symptomatology. The etiology remains unknown. Either spontaneous dominant mutations or de novo chromosomal rearrangements have been proposed as possible explanations. In addition to its clinical triad of RES, parietal alopecia, and trigeminal anesthesia, CTD dysplasia is associated with a wide range of phenotypic and neurodevelopmental abnormalities.Treatment is symptomatic and includes physical rehabilitation, special education, dental care, and ocular protection against self-induced corneal trauma that causes ulcers and, later, corneal opacification. The prognosis is correlated to the mental development, motor handicap, corneal–facial anesthesia, and visual problems. Follow-up on a large number of patients with CTD dysplasia has never been reported and experience is limited to few cases to date. High degree of suspicion in a child presenting with characteristic alopecia and RES has a great importance in diagnosis of this syndrome.

scholarly journals Autism Spectrum Disorder in a Girl with aDe NovoX;19 Balanced Translocation

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Marcelo Razera Baruffi ◽  
Deise Helena de Souza ◽  
Rosana Aparecida Bicudo da Silva ◽  
Ester Silveira Ramos ◽  
Danilo Moretti-Ferreira
Keyword(s):  
X Chromosome ◽  
De Novo ◽  
Recurrent Miscarriage ◽  
Chromosomal Rearrangements ◽  
Position Effect ◽  
Autism Spectrum ◽  
Balanced Translocation ◽  
Replication Banding ◽  
Conventional Cytogenetic Analysis ◽  
Gonadal Dysfunction

Balanced X-autosome translocations are rare, and female carriers are a clinically heterogeneous group of patients, with phenotypically normal women, history of recurrent miscarriage, gonadal dysfunction, X-linked disorders or congenital abnormalities, and/or developmental delay. We investigated a patient with ade novoX;19 translocation. The six-year-old girl has been evaluated due to hyperactivity, social interaction impairment, stereotypic and repetitive use of language with echolalia, failure to follow parents/caretakers orders, inconsolable outbursts, and persistent preoccupation with parts of objects. The girl has normal cognitive function. Her measurements are within normal range, and no other abnormalities were found during physical, neurological, or dysmorphological examinations. Conventional cytogenetic analysis showed ade novobalanced translocation, with the karyotype 46,X,t(X;19)(p21.2;q13.4). Replication banding showed a clear preference for inactivation of the normal X chromosome. The translocation was confirmed by FISH and Spectral Karyotyping (SKY). Although abnormal phenotypes associated withde novobalanced chromosomal rearrangements may be the result of disruption of a gene at one of the breakpoints, submicroscopic deletion or duplication, or a position effect, X; autosomal translocations are associated with additional unique risk factors including X-linked disorders, functional autosomal monosomy, or functional X chromosome disomy resulting from the complex X-inactivation process.

scholarly journals The Genomic Architecture of a Rapid Island Radiation: Recombination Rate Variation, Chromosome Structure, and Genome Assembly of the Hawaiian Cricket Laupala

2017 ◽  
Author(s):  
Thomas Blankers ◽  
Kevin P. Oh ◽  
Aureliano Bombarely ◽  
Kerry L. Shaw
Keyword(s):  
Large Scale ◽  
De Novo ◽  
Chromosomal Rearrangements ◽  
Evolutionary Genetics ◽  
Rate Variation ◽  
Linkage Maps ◽  
Recombination Rates ◽  
Behavioral Isolation ◽  
Genomic Architecture ◽  
Suppressed Recombination

ABSTRACTPhenotypic evolution and speciation depend on recombination in many ways. Within populations, recombination can promote adaptation by bringing together favorable mutations and decoupling beneficial and deleterious alleles. As populations diverge, cross-over can give rise to maladapted recombinants and impede or reverse diversification. Suppressed recombination due to genomic rearrangements, modifier alleles, and intrinsic chromosomal properties may offer a shield against maladaptive gene flow eroding co-adapted gene complexes. Both theoretical and empirical results support this relationship. However, little is known about this relationship in the context of behavioral isolation, where co-evolving signals and preferences are the major hybridization barrier. Here we examine the genomic architecture of recently diverged, sexually isolated Hawaiian swordtail crickets (Laupala). We assemble a de novo genome and generate three dense linkage maps from interspecies crosses. In line with expectations based on the species’ recent divergence and successful interbreeding in the lab, the linkage maps are highly collinear and show no evidence for large-scale chromosomal rearrangements. The maps were then used to anchor the assembly to pseudomolecules and estimate recombination rates across the genome. We tested the hypothesis that loci involved in behavioral isolation (song and preference divergence) are in regions of low interspecific recombination. Contrary to our expectations, a genomic region where a male song QTL co-localizes with a female preference QTL was not associated with particularly low recombination rates. This study provides important novel genomic resources for an emerging evolutionary genetics model system and suggests that trait-preference co-evolution is not necessarily facilitated by locally suppressed recombination.

scholarly journals Risks and Recommendations in Prenatally Detected De Novo Balanced Chromosomal Rearrangements from Assessment of Long-Term Outcomes

2018 ◽  
Vol 102 (6) ◽  
pp. 1090-1103 ◽  
Author(s):  
Christina Halgren ◽  
Nete M. Nielsen ◽  
Lusine Nazaryan-Petersen ◽  
Asli Silahtaroglu ◽  
Ryan L. Collins ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Long Term Outcomes

Complex Chromosomal Rearrangements

2018 ◽  
Author(s):  
R. J McKinlay Gardner ◽  
David J Amor
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Chromosome Rearrangements ◽  
Type I ◽  
Complex Type ◽  
Reproductive Risk ◽  
Clinically Normal ◽  
Complex Chromosomal Rearrangements ◽  
Very High ◽  
Complex Chromosome

Complex chromosome rearrangements (CCRs) include most of the rearrangements that would not be accounted for as “straightforward” classical categories. They may be translocations with three or more segments involved; or they may comprise a mix of translocation and, for example, inversion. Some can be extraordinarily complex. CCRs are classified as types I–IV, most falling into the “least complex” type I category, while types II–IV are grouped as “exceptional CCRs.” Many unbalanced CCRs have arisen de novo and imply no increased reproductive risk. The identification of the clinically normal balanced CCR carrier is less frequent, and for these people, the reproductive risks can be very high.

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