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1.
Fertil Steril ; 116(5): 1203-1204, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34756325

RESUMO

This month's Views and Reviews focuses on different aspects of the diagnosis of mosaicism. The first piece was written by Treff and Marin, who discuss the methodologic challenges of preimplantation genetic testing for aneuploidies and how the diagnosis of "mosaic" has led to a significant reduction in the accuracy of such testing. The second article by Viotti et al. provides an excellent overview of outcome data from >1,000 mosaic embryo transfers. The investigators make a strong case for three categorizations of embryos: euploid, aneuploid, and mosaic, and that use of mosaic embryos will prevent the discard of embryos that may lead to live birth. The final piece in this series was written by Besser et al., who discussed the various society recommendations for genetic counseling and prenatal diagnostic testing after mosaic embryo transfer and question whether these are truly data-driven. This collection of pieces will give the reader a deeper understanding of the controversy and management of mosaic embryo transfer.


Assuntos
Blastocisto/patologia , Testes Genéticos , Infertilidade/terapia , Mosaicismo , Diagnóstico Pré-Natal , Técnicas de Reprodução Assistida/efeitos adversos , Aneuploidia , Transferência Embrionária , Feminino , Aconselhamento Genético , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Masculino , Valor Preditivo dos Testes , Gravidez , Reprodutibilidade dos Testes , Resultado do Tratamento
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(11): 1097-1100, 2021 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-34729751

RESUMO

OBJECTIVE: To report on a family which has two siblings with SCN2A mutation caused by germline mosaicism suffering from autism spectrum disorder/development delay (ASD/DD). METHODS: Clinical data was collected for the proband and his parents. Next generation sequencing (NGS) was carried out on the proband and his parents. Suspected mutations were verified by Sanger sequencing of the proband, his parents and brother. To detect whether there is a low proportion of somatic mosaicism in the parents, a droplet digital PCR was conducted. The result of ddPCR showed that the father was germline mosaicism (0.233%). RESULTS: NGS has identified a de novo splicing mutation of the SCN2A gene, c.605+1G>A, in the proband and his brother. Combined with its clinical phenotype and inheritance pattern, SCN2A was judged to be the pathogenic gene. Above findings strongly suggested parental germline mosaicism. CONCLUSION: ASD/DD in siblings with SCN2A mutations caused by germline mosaicism. Paternal mosaicism should be considered as one of the important inheritance patterns for counseling parents with a child carrying SCN2A mutation. The ddPCR can help to reveal very low proportion of germline mosaicism.


Assuntos
Transtorno do Espectro Autista , Irmãos , Células Germinativas , Humanos , Masculino , Mosaicismo , Mutação , Canal de Sódio Disparado por Voltagem NAV1.2/genética
3.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(12): 1250-1253, 2021 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-34839518

RESUMO

OBJECTIVE: To carry out genetic analysis and parental tracing for a fetus with an inconclusive chromosomal karyotype. METHODS: The fetus and its parents were subjected to combined chromosomal karyotyping, chromosomal microarray analysis (CMA), fluorescence in situ hybridization (FISH) and multiplex PCR testing for Y chromosome microdeletions. RESULTS: The fetus was found to have a karyotype of 45,X[18]/46,X,+mar[72]. CMA revealed that the fetus has carried a 2.6 Mb duplication at Yp11.32p11.31 and a 44.5 Mb deletion at Yq11.21q12. Interphase FISH of amniocytes confirmed the chromosomal mosaicism in the fetus, which has derived from Y chromosome. Multiplex PCR revealed deletion of AZFb and AZFc regions on the Y chromosome. No karyotypic abnormality was found with either parent at 400-band level. CONCLUSION: Combined genetic analysis has delineated the aberrant karyotype in the fetus, which has facilitated prediction of its clinical phenotype and genetic counseling.


Assuntos
Mosaicismo , Diagnóstico Pré-Natal , Cromossomos Humanos Y/genética , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Cariótipo , Gravidez
4.
J Equine Vet Sci ; 105: 103720, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34607685

RESUMO

A 4-year-old Colombian Creole mare was presented for diagnosis because the external orifice of her cervix was not detectable when a uterine lavage as therapy for uterine fluid accumulation was attempted. Clinical and ultrasonographic evaluation of the genital tract revealed that ovaries were of normal size and showed structures suggestive of regular ovarian activity. However, granular free-floating fluid material distending the uterus was detected by ultrasound. Upon vaginal examination, the normal external cervical morphology was not evident. The vagina ended in a blind bag with a small papilla with no evident external cervical os. Cytology of uterine fluid obtained by transvaginal aspiration showed findings compatible with mucometra. Cytogenetic analysis revealed an abnormal karyotype (63,X and 64,XX both 45% and 65,XXX 10%). A diagnosis of congenital segmental cervical aplasia was proposed possibly related to the mosaicism detected. To our knowledge, this is the first case of this reproductive pathology in a mare with regular ovarian activity and confirmed aneuploidy in mosaic form of the X sex chromosome.


Assuntos
Doenças dos Cavalos , Útero , Aneuploidia , Animais , Colômbia , Feminino , Cavalos , Mosaicismo , Cromossomo X
5.
Fertil Steril ; 116(5): 1212-1219, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34627598

RESUMO

Chromosomal mosaicism, the coexistence of cells with different chromosomal content, has been documented in human embryos for 3 decades. Early versions of preimplantation genetic testing for aneuploidy (PGT-A) did not measure mosaicism, either because typically only a single cell was assessed or because the technique could not accurately identify it. Although this led to a straightforward diagnosis (an embryo was considered either normal or abnormal), it simply avoided the issue and, in hindsight, may have led to numerous misdiagnoses with negative clinical consequences. Modern PGT-A evaluates a multicellular biopsy specimen with techniques capable of recognizing intermediate copy number signals for chromosomes or subchromosomal regions. We are, therefore, inevitably confronted with the issue of mosaicism and the challenge of managing embryos producing such results in the clinic. Here we discuss recent data showing that not only mosaicism in general, but specific features of mosaicism detected with PGT-A, are associated with variable clinical outcomes. The conclusion is evident: mosaicism should be considered for more informed and improved embryo selection in the clinic.


Assuntos
Blastocisto/patologia , Testes Genéticos , Infertilidade/terapia , Mosaicismo , Diagnóstico Pré-Natal , Técnicas de Reprodução Assistida/efeitos adversos , Aneuploidia , Transferência Embrionária , Feminino , Aconselhamento Genético , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Masculino , Valor Preditivo dos Testes , Gravidez , Reprodutibilidade dos Testes , Resultado do Tratamento
6.
Behav Brain Sci ; 44: e103, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34588033

RESUMO

Mehr et al. seek to explain music's evolution in terms of a unitary proper function - signalling cooperative intent - which they cash out in two guises, coalition signalling and (allo)parental attention signalling. Although we recognize the role signalling almost certainly played in the evolution of music, we reject "ultimate" causal explanations which focus on a unidirectional, narrow range of causal factors.


Assuntos
Música , Atenção , Humanos , Mosaicismo
7.
Virus Res ; 305: 198553, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34487767

RESUMO

COVID-19 is seriously threatening human health all over the world. A comprehensive understanding of the genetic mechanisms driving the rapid evolution of its pathogen (SARS-CoV-2) is the key to controlling this pandemic. In this study, by comparing the entire genome sequences of SARS-CoV-2 isolates from Asia, Europe and America, and analyzing their phylogenetic histories, we found a lineage derived from a recombination event that likely occurred before March 2020. More importantly, the recombinant offspring has become the dominant strain responsible for more than one-third of the global cases in the pandemic. These results indicated that the recombination might have played a key role in the pandemic of the virus.


Assuntos
COVID-19/epidemiologia , Evolução Molecular , Genoma Viral , Recombinação Homóloga , Mosaicismo , SARS-CoV-2/genética , América/epidemiologia , Ásia/epidemiologia , Sequência de Bases , COVID-19/história , COVID-19/transmissão , COVID-19/virologia , Europa (Continente)/epidemiologia , Genômica/métodos , História do Século XXI , Humanos , Mutação , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/patogenicidade
9.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360897

RESUMO

Inherited cardiomyopathies are among the major causes of heart failure and associated with significant mortality and morbidity. Currently, over 70 genes have been linked to the etiology of various forms of cardiomyopathy, some of which are X-linked. Due to the lack of appropriate cell and animal models, it has been difficult to model these X-linked cardiomyopathies. With the advancement of induced pluripotent stem cell (iPSC) technology, the ability to generate iPSC lines from patients with X-linked cardiomyopathy has facilitated in vitro modelling and drug testing for the condition. Nonetheless, due to the mosaicism of the X-chromosome inactivation, disease phenotypes of X-linked cardiomyopathy in heterozygous females are also usually more heterogeneous, with a broad spectrum of presentation. Recent advancements in iPSC procedures have enabled the isolation of cells with different lyonisation to generate isogenic disease and control cell lines. In this review, we will summarise the current strategies and examples of using an iPSC-based model to study different types of X-linked cardiomyopathy. The potential application of isogenic iPSC lines derived from a female patient with heterozygous Danon disease and drug screening will be demonstrated by our preliminary data. The limitations of an iPSC-derived cardiomyocyte-based platform will also be addressed.


Assuntos
Genes Ligados ao Cromossomo X , Doença de Depósito de Glicogênio Tipo IIb/genética , Doença de Depósito de Glicogênio Tipo IIb/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Diferenciação Celular , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Doença de Depósito de Glicogênio Tipo IIb/classificação , Doença de Depósito de Glicogênio Tipo IIb/patologia , Heterozigoto , Humanos , Masculino , Mosaicismo , Inativação do Cromossomo X
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 771-774, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365622

RESUMO

OBJECTIVE: To review the clinical data of a fetus with false positive result of non-invasive prenatal testing (NIPT) due to confined placental mosaicism (CPM). METHODS: Amniotic fluid sample was taken from a pregnant women with high risk for chromosome 16 aneuploidy for karyotyping analysis, single nucleotide polymorphism array (SNP array) and interphase fluorescence in situ hybridization (FISH). Genetic testing was also conducted on the fetal and maternal surface of the placenta, root of umbilical cord and fetal skin tissue after induced abortion. RESULTS: Cytogenetic analysis of the amniotic fluid sample yielded a normal karyotype. SNP array revealed mosaicism (20%) of trisomy 16 in the fetus. FISH confirmed the presence of mosaicism (25%) for trisomy 16. After induced labor, all sampled sites of placenta were confirmed to contain trisomy 16 by SNP array, while the analysis of fetal skin tissue yielded a negative result. CONCLUSION: CPM is an important factor for false positive NIPT result. Prenatal identification of CPM and strengthened pregnancy management are important to reduce adverse pregnancy outcomes.


Assuntos
Cromossomos Humanos Par 16 , Mosaicismo , Amniocentese , Cromossomos Humanos Par 16/genética , Análise Citogenética , Feminino , Feto , Humanos , Hibridização in Situ Fluorescente , Biologia Molecular , Placenta , Gravidez , Diagnóstico Pré-Natal , Trissomia/genética
11.
Nature ; 597(7876): 387-392, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34433963

RESUMO

Starting from the zygote, all cells in the human body continuously acquire mutations. Mutations shared between different cells imply a common progenitor and are thus naturally occurring markers for lineage tracing1,2. Here we reconstruct extensive phylogenies of normal tissues from three adult individuals using whole-genome sequencing of 511 laser capture microdissections. Reconstructed embryonic progenitors in the same generation of a phylogeny often contribute to different extents to the adult body. The degree of this asymmetry varies between individuals, with ratios between the two reconstructed daughter cells of the zygote ranging from 60:40 to 93:7. Asymmetries pervade subsequent generations and can differ between tissues in the same individual. The phylogenies resolve the spatial embryonic patterning of tissues, revealing contiguous patches of, on average, 301 crypts in the adult colonic epithelium derived from a most recent embryonic cell and also a spatial effect in brain development. Using data from ten additional men, we investigated the developmental split between soma and germline, with results suggesting an extraembryonic contribution to primordial germ cells. This research demonstrates that, despite reaching the same ultimate tissue patterns, early bottlenecks and lineage commitments lead to substantial variation in embryonic patterns both within and between individuals.


Assuntos
Linhagem da Célula/genética , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Desenvolvimento Embrionário/genética , Mutação , Encéfalo/metabolismo , Cromossomos Humanos Y/genética , Células Clonais/metabolismo , Mutação em Linhagem Germinativa/genética , Humanos , Masculino , Mosaicismo , Especificidade de Órgãos/genética , Polimorfismo de Nucleotídeo Único/genética
12.
Fertil Steril ; 116(5): 1220-1224, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34373104

RESUMO

Mosaic results obtained through preimplantation genetic testing for aneuploidy pose ongoing challenges to clinical practice. Thorough genetic counseling for patients considering mosaic embryo transfer is consistently recommended by many best-practice statements, and providers are charged with the task of assessing and explaining potential prenatal, neonatal, and long-term risks. However, an increasing amount of outcome data from transferred embryos with mosaic results do not show any evidence of increased risk to ongoing pregnancies or newborns. This article examines how to reconcile these data with the current practices for patient education about preimplantation genetic testing for aneuploidy and mosaic embryo risk assessment, through an evidence-based lens.


Assuntos
Blastocisto/patologia , Testes Genéticos , Infertilidade/terapia , Mosaicismo , Diagnóstico Pré-Natal , Técnicas de Reprodução Assistida/efeitos adversos , Aneuploidia , Transferência Embrionária , Feminino , Aconselhamento Genético , Humanos , Infertilidade/diagnóstico , Infertilidade/fisiopatologia , Masculino , Valor Preditivo dos Testes , Gravidez , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Resultado do Tratamento
13.
Andrologia ; 53(11): e14213, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34375016

RESUMO

Patients with Klinefelter syndrome (KS) show a typically 47,XXY karyotype; however, some variations have been observed, including 47,XX,der(Y), 46,XY/47,XXY, 48,XXXY, 48,XXYY, and mosaicism or structural sex chromosome abnormalities in some patients. In the literature, a rare KS variant, 47,X,del(Xq),Y karyotype, was reported in only a few cases prior to 1981. A 40-year-old man (IV-3) was referred to our department due to infertility. His phenotype did not differ from the classic KS phenotype. He had two siblings (1-male; 1-female). His brother (IV-5) had mental retardation and died one year earlier at age 32. Additionally, his sister (IV-2) also had a history of infertility due to her husband's azoospermia. His mother had a history of 12 miscarriages. Karyotype analysis revealed the 47,X,del(Xq24),Y karyotype, and no deletions were seen in the AZF and SRY regions. We thought this chromosomal abnormality in the patient might have resulted from X-autosome translocation in one of his parents since his mother had recurrent pregnancy loss and his sibling had mental retardation. However, we could not confirm it due to his parents were not alive. This study shows the first case of a long-arm X-chromosome deletion after a long period and reviews current knowledge concerning variant KS (deletion Xq).


Assuntos
Azoospermia , Síndrome de Klinefelter , Adulto , Feminino , Humanos , Cariotipagem , Síndrome de Klinefelter/genética , Masculino , Mosaicismo , Aberrações dos Cromossomos Sexuais
14.
Hum Genet ; 140(11): 1581-1591, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34370083

RESUMO

One of the most unique coat color patterns in the domestic dog is merle (also known as dapple in the dachshund breed), characterized by patches of normal pigmentation surrounded by diluted eumelanin pigment. In dogs, this striking variegated pattern is caused by an insertion of a SINE element into the PMEL gene. Differences in the length of the SINE insertion [due to a variable-length poly(A)-tail] has been associated with variation in the merle coat color and patterning. We previously performed a systematic evaluation of merle in 175 Australian shepherds and related breeds and correlated the length of the merle insertion variants with four broad phenotypic clusters designated as "cryptic", "atypical", "classic", and "harlequin" merle. In this study, we evaluated the SINE insertions in 140 dachshunds and identified the same major merle phenotypic clusters with only slight variation between breeds. Specifically, we identified numerous cases of true "hidden" merle in dachshunds with light/red (pheomelanin) coats with little to no black/brown pigment (eumelanin) and thus minimal or no observable merle phenotype. In addition, we identified somatic and gonadal mosaicism, with one dog having a large insertion in the harlequin size range of M281 that had no merle phenotype and unintentionally produced a double merle puppy with anophthalmia. The frequent identification of cryptic, hidden, and mosaic merle variants, which can be undetectable by phenotypic inspection, should be of particular concern to breeders and illustrates the critical need for genetic testing for merle prior to breeding to avoid producing dogs with serious health problems.


Assuntos
Pelo Animal/anatomia & histologia , Cães/genética , Testes Genéticos/veterinária , Cor de Cabelo/genética , Antígeno gp100 de Melanoma/genética , Alelos , Animais , Cruzamento , Cães/anatomia & histologia , Feminino , Estudos de Associação Genética , Genótipo , Masculino , Melaninas/genética , Mosaicismo , Mutação , Linhagem , Fenótipo , Elementos Nucleotídeos Curtos e Dispersos
15.
Nat Commun ; 12(1): 4178, 2021 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-34234147

RESUMO

Mosaic loss of chromosome Y (LOY) in leukocytes is the most common form of clonal mosaicism, caused by dysregulation in cell-cycle and DNA damage response pathways. Previous genetic studies have focussed on identifying common variants associated with LOY, which we now extend to rarer, protein-coding variation using exome sequences from 82,277 male UK Biobank participants. We find that loss of function of two genes-CHEK2 and GIGYF1-reach exome-wide significance. Rare alleles in GIGYF1 have not previously been implicated in any complex trait, but here loss-of-function carriers exhibit six-fold higher susceptibility to LOY (OR = 5.99 [3.04-11.81], p = 1.3 × 10-10). These same alleles are also associated with adverse metabolic health, including higher susceptibility to Type 2 Diabetes (OR = 6.10 [3.51-10.61], p = 1.8 × 10-12), 4 kg higher fat mass (p = 1.3 × 10-4), 2.32 nmol/L lower serum IGF1 levels (p = 1.5 × 10-4) and 4.5 kg lower handgrip strength (p = 4.7 × 10-7) consistent with proposed GIGYF1 enhancement of insulin and IGF-1 receptor signalling. These associations are mirrored by a common variant nearby associated with the expression of GIGYF1. Our observations highlight a potential direct connection between clonal mosaicism and metabolic health.


Assuntos
Proteínas de Transporte/genética , Cromossomos Humanos Y/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Mosaicismo , Adulto , Idoso , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Análise Mutacional de DNA , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Insulina/metabolismo , Leucócitos , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais/genética , Sequenciamento Completo do Exoma
16.
F1000Res ; 10: 148, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34164111

RESUMO

Neurofibromatosis 1 (NF1) is a neurocutaneous syndrome characterized by multiple café-au-lait macules, cutaneous neurofibromas or plexiform neurofibromas, iris Lisch nodules, axillary and inguinal freckling. Mosaicism in NF1 can either present as a generalized disease, or in a localized (segmental) manner. Mosaic generalized NF1 may have presentations that are similar to generalized NF1 or have a milder phenotype and hence may be under-recognised in clinical practice. We report a nonsense mutation in the NF1 gene in a 55-year old Chinese male with the mosaic generalized phenotype. He reported noticing increasing numbers of skin-colored papules over his face, neck, back and abdomen when he was about 40 years old. From both next-generation and Sanger sequencing data, the variant appeared to be mosaic and present at about 24%. It is in exon 39 and has not been reported in any database or published literature.


Assuntos
Neurofibromatose 1 , Neurofibromina 1 , Adulto , Códon sem Sentido , Genes da Neurofibromatose 1 , Humanos , Masculino , Pessoa de Meia-Idade , Mosaicismo , Neurofibromatose 1/genética , Neurofibromina 1/genética , Fenótipo
17.
Orv Hetil ; 162(29): 1156-1165, 2021 07 18.
Artigo em Húngaro | MEDLINE | ID: mdl-34274918

RESUMO

Összefoglaló. Bevezetés és célkituzés: A gyakori autoszomális trisomiák és a nemi kromoszómaeltérések a mikroszkóppal észlelheto kromoszóma-rendellenességek kb. 80-85%-át képviselik. A ritka kromoszóma-rendellenességek klinikai következménye jelentos, kimutatásukat a jelenlegi szurovizsgálatok ugyan nem célozzák, de a teljes kromoszómaszerelvényt vizsgáló, nem invazív praenatalis tesztelés új lehetoséget nyitott a korai felismerésükre. Módszer: Retrospektív analízis (2014-2019) a mikroszkóppal kimutatható kromoszóma-rendellenességek eloszlására, a fetoplacentaris mozaikosság elofordulására, klinikai összefüggéseire a praenatalis vizsgálatok tükrében egy hazai tercier centrumban. Eredmények: 2504 invazív beavatkozást végeztünk és 200 kromoszómaeltérést mutattunk ki (8%), melyek közül újonnan kialakult, ritka rendellenesség 27 volt (13,5%). Ritka autoszomális trisomia 14, poliploidia 6, de novo szerkezeti kromoszómaeltérés 5, marker kromoszóma 2 esetben igazolódott. A fetoplacentaris mozaikosság aránya a gyakori/ritka kromoszómaeltérésekben 12,4%/77,8% volt (p = 0,001), 17/40 esetben lepényre korlátozódott. A gyakori trisomiákkal kóros tarkóredo-vastagság 58%-ban, major ultrahangeltérés 35%-ban társult, melyek jelentosen különböztek a ritka kromoszómaeltérésekben (11%, p = 0,006; 67%, p = 0,047). A ritka kromoszómaeltérések jellemzo praenatalis major ultrahangeltérése a facialis dysmorphismus volt. A teljes kromoszómaszerelvényt vizsgáló praenatalis tesztelés a ritka kromoszómaeltérések 12 lepényi mozaikos esetében (44%) feltételezhetoen álpozitív, 1 esetben (3,7%) álnegatív eredményt generált volna, miközben a ritka autoszomális trisomiák 2 esetében ultrahangeltérés nélkül is korán detektálta volna a ritka magzati kromoszómaeltérést (7,4%). Következtetés: A normális tarkóredo-vastagság esetén észlelt major ultrahangeltérések felhívhatják a figyelmet a döntoen mozaikos ritka kromoszóma-rendellenességekre. A teljes kromoszómaszerelvényt vizsgáló, nem invazív szuroteszt a korai diagnosztika alternatívája lehet, a mozaikosságból adódó álpozitív eredményekre azonban számítani kell. A fetoplacentaris mozaikosság ismerete fontos klinikai információt biztosít, mely befolyásolhatja a terhesség kimenetelét, a terhesség követésének módját. A pontos citogenetikai karakterizálás elengedhetetlen. Orv Hetil. 2021; 162(29): 1156-1165. INTRODUCTION AND OBJECTIVE: To determine the prevalence of microscopically visible de novo atypical chromosomal aberrations and fetoplacental mosaicism in a prenatal tertial referral center, and to investigate the maternal and fetal characteristics in connection with genomewide non-invasive prenatal screening. METHOD: Retrospective cohort study from 2014 to 2019 of pregnancies with invasive genetic analysis. RESULTS: In the cohort of 2504 cases, the proportion of CVS was 53.3%. We diagnosed 200 chromosomal aberrations (8%), including 13.5% of de novo rare chromosomal aberrations (14 rare autosomal trisomies, 6 polyploidies, 5 structural aberrations and 2 small supernumerary marker chromosomes). The rate of fetoplacental mosaicism was 12.4%/77.8% in common/atypical chromosomal aberrations (p = 0.001) and confined to placenta in 17/40 cases. Associated ultrasound abnormalities were abnormal nuchal translucency and major malformations in 58% and 35% with common trisomies and 11% (p = 0.006) and 67% (p = 0.047) with true mosaic cases of rare abnormalities, respectively. Major ultrasound malformation was facial dysmorphism with rare aberrations. Potential application of genomewide non-invasive prenatal test in atypical chromosomal aberrations presumably would have been false-positive in 12 cases (44%), false-negative in 1 case (3.7%), and would have early detected 2 cases of rare autosomal trisomies (7.4%) without ultrasound anomalies. CONCLUSION: Structural ultrasound malformations with normal nuchal translucency thickness may be indicative of rare chromosomal aberrations. Application of genomewide non-invasive prenatal test is an alternative of early diagnostic methods with a potential of discordant results due to mosaicism. Knowledge about the presence of fetoplacental mosaicism influences risk estimation and genetic counseling, detailed cytogenetic characterization is of utmost importance. Orv Hetil. 2021; 162(29): 1156-1165.


Assuntos
Mosaicismo , Diagnóstico Pré-Natal , Feminino , Humanos , Masculino , Gravidez , Prevalência , Estudos Retrospectivos , Ultrassonografia
18.
Biomed Res Int ; 2021: 6258527, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307659

RESUMO

Small supernumerary marker chromosomes (sSMCs) are a group of rare chromosomal anomalies, which pose challenges in the clinical practice of prenatal diagnosis and genetic counseling. This study enrolled an extended family with an underage male patient displaying infantile seizures, intellectual disability, and retarded speech and psychomotor function. A series of multiplatform genetic detections was conducted to explore the diagnostic variation. Whole exome sequencing (WES) and chromosomal microarray analysis (CMA) indicated a mosaic sSMC derived from the pericentromeric region of chromosome 8 in the patient, which was confirmed using cytogenetic methods. The proband and his mother, who carried this mosaic variant, exhibited strong phenotypic variability. We also ruled out the pathogenicity of a KDM5C variant by extended validation. Our results emphasized the capacity of WES to detect mosaic SMCs and the importance of mosaic ratios in the appearance and severity of symptomatic phenotypes.


Assuntos
Cromossomos Humanos/genética , Mosaicismo , Sequenciamento Completo do Exoma , Adulto , Sequência de Bases , Centrômero/genética , Pré-Escolar , Análise Citogenética , Família , Marcadores Genéticos , Humanos , Masculino , Mutação/genética , Reprodutibilidade dos Testes
20.
Cytogenet Genome Res ; 161(5): 243-248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34265761

RESUMO

A female cynomolgus monkey (Macaca fascicularis) with facial features characteristic of Down syndrome showed abnormal behavior, unwariness toward humans, and poor concentration. The number of metaphase chromosomes in blood lymphocytes was examined and found to be 43, which indicated one extra chromosome to the normal diploid number (2n = 42). We then used Q-banding and multicolor FISH techniques to identify the extra chromosome. The results revealed an additional chromosome 17, with no other chromosomal rearrangements, such as translocations. Since no mosaicism or heterozygous variant chromosomes were observed, full trisomy 17 was assessed in this female cynomolgus monkey. Chromosome 17 corresponds to human chromosome 13, and human trisomy 13, known as Patau syndrome, results in severe clinical signs and, often, a short life span; however, this individual has reached an age of 10 years with only mild clinical signs. Although genomic differences exist between human and macaques, this individual's case could help to reveal the pathological and genetic mechanisms of Patau syndrome.


Assuntos
Cromossomos de Mamíferos/ultraestrutura , Macaca fascicularis/genética , Animais , Bandeamento Cromossômico , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 17 , Feminino , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Macaca fascicularis/anormalidades , Mosaicismo/veterinária , Especificidade da Espécie , Trissomia , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomia do Cromossomo 13/patologia
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