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1.
Pediatr Blood Cancer ; 71(9): e31129, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38952259

RESUMO

BACKGROUND: The objective of this study is to assess the concordance and added value of combined comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH/SNP) analyses in pediatric acute lymphoblastic leukemia (ALL) risk stratification compared to conventional cytogenetic methods. PROCEDURE: This is a retrospective study that included patients aged 1-18 years diagnosed with de novo ALL at Sainte-Justine Hospital between 2016 and 2021. Results from conventional cytogenetic and molecular analyses were collected and compared to those of CGH/SNP. RESULTS: A total of 135 ALL patients were included. Sample failures or non-diagnostic analyses occurred in 17.8% cases with G-banding karyotypes versus 1.5% cases with CGH/SNP. The mean turnaround time for results was significantly faster for CGH/SNP than karyotype with 5.8 versus 10.7 days, respectively. The comparison of ploidy assessment by CGH/SNP and G-banding karyotype showed strong concordance (r = .82, p < .001, r2 = .68). Furthermore, G-banding karyotype did not detect additional clinically relevant aberrations that were missed by the combined analysis of CGH/SNP and fluorescence in situ hybridization. The most common gene alterations detected by CGH/SNP were deletions involving CDKN2A (35.8%), ETV6 (31.3%), CDKN2B (28.4%), PAX5 (20.1%), IKZF1 (12.7%), and copy-neutral loss of heterozygosity (CN-LOH) of 9p (9.0%). Among these, only ETV6 deletion was found to have a significant prognostic impact with superior event-free survival in both univariate and multivariate analyses (adjusted hazard ratio 0.08, 95% confidence interval: 0.01-0.50, p = .02). CONCLUSION: CGH/SNP provided faster, reliable, and highly concordant results than those obtained by conventional cytogenetics. CGH/SNP identified recurrent gene deletions in pediatric ALL, of which ETV6 deletion conferred a favorable prognosis.


Assuntos
Hibridização Genômica Comparativa , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Feminino , Pré-Escolar , Masculino , Adolescente , Lactente , Estudos Retrospectivos , Hibridização Genômica Comparativa/métodos , Prognóstico , Medição de Risco/métodos , Seguimentos , Taxa de Sobrevida
2.
Mol Psychiatry ; 26(6): 2663-2676, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33414497

RESUMO

Genomic copy number variants (CNVs) are routinely identified and reported back to patients with neuropsychiatric disorders, but their quantitative effects on essential traits such as cognitive ability are poorly documented. We have recently shown that the effect size of deletions on cognitive ability can be statistically predicted using measures of intolerance to haploinsufficiency. However, the effect sizes of duplications remain unknown. It is also unknown if the effect of multigenic CNVs are driven by a few genes intolerant to haploinsufficiency or distributed across tolerant genes as well. Here, we identified all CNVs > 50 kilobases in 24,092 individuals from unselected and autism cohorts with assessments of general intelligence. Statistical models used measures of intolerance to haploinsufficiency of genes included in CNVs to predict their effect size on intelligence. Intolerant genes decrease general intelligence by 0.8 and 2.6 points of intelligence quotient when duplicated or deleted, respectively. Effect sizes showed no heterogeneity across cohorts. Validation analyses demonstrated that models could predict CNV effect sizes with 78% accuracy. Data on the inheritance of 27,766 CNVs showed that deletions and duplications with the same effect size on intelligence occur de novo at the same frequency. We estimated that around 10,000 intolerant and tolerant genes negatively affect intelligence when deleted, and less than 2% have large effect sizes. Genes encompassed in CNVs were not enriched in any GOterms but gene regulation and brain expression were GOterms overrepresented in the intolerant subgroup. Such pervasive effects on cognition may be related to emergent properties of the genome not restricted to a limited number of biological pathways.


Assuntos
Variações do Número de Cópias de DNA , Genoma , Cognição , Variações do Número de Cópias de DNA/genética , Dosagem de Genes , Humanos , Testes de Inteligência
3.
J Med Genet ; 55(4): 215-221, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29496978

RESUMO

BACKGROUND: The aim of this guideline is to provide updated recommendations for Canadian genetic counsellors, medical geneticists, maternal fetal medicine specialists, clinical laboratory geneticists and other practitioners regarding the use of chromosomal microarray analysis (CMA) for prenatal diagnosis. This guideline replaces the 2011 Society of Obstetricians and Gynaecologists of Canada (SOGC)-Canadian College of Medical Geneticists (CCMG) Joint Technical Update. METHODS: A multidisciplinary group consisting of medical geneticists, genetic counsellors, maternal fetal medicine specialists and clinical laboratory geneticists was assembled to review existing literature and guidelines for use of CMA in prenatal care and to make recommendations relevant to the Canadian context. The statement was circulated for comment to the CCMG membership-at-large for feedback and, following incorporation of feedback, was approved by the CCMG Board of Directors on 5 June 2017 and the SOGC Board of Directors on 19 June 2017. RESULTS AND CONCLUSIONS: Recommendations include but are not limited to: (1) CMA should be offered following a normal rapid aneuploidy screen when multiple fetal malformations are detected (II-1A) or for nuchal translucency (NT) ≥3.5 mm (II-2B) (recommendation 1); (2) a professional with expertise in prenatal chromosomal microarray analysis should provide genetic counselling to obtain informed consent, discuss the limitations of the methodology, obtain the parental decisions for return of incidental findings (II-2A) (recommendation 4) and provide post-test counselling for reporting of test results (III-A) (recommendation 9); (3) the resolution of chromosomal microarray analysis should be similar to postnatal microarray platforms to ensure small pathogenic variants are detected. To minimise the reporting of uncertain findings, it is recommended that variants of unknown significance (VOUS) smaller than 500 Kb deletion or 1 Mb duplication not be routinely reported in the prenatal context. Additionally, VOUS above these cut-offs should only be reported if there is significant supporting evidence that deletion or duplication of the region may be pathogenic (III-B) (recommendation 5); (4) secondary findings associated with a medically actionable disorder with childhood onset should be reported, whereas variants associated with adult-onset conditions should not be reported unless requested by the parents or disclosure can prevent serious harm to family members (III-A) (recommendation 8).The working group recognises that there is variability across Canada in delivery of prenatal testing, and these recommendations were developed to promote consistency and provide a minimum standard for all provinces and territories across the country (recommendation 9).


Assuntos
Aconselhamento Genético , Guias de Prática Clínica como Assunto , Diagnóstico Pré-Natal/métodos , Natimorto , Criança , Feminino , Feto/fisiopatologia , Testes Genéticos , Humanos , Gravidez , Cuidado Pré-Natal
4.
Genes Chromosomes Cancer ; 57(6): 311-319, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29427526

RESUMO

The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60%-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners. We report a novel NUP98-BPTF fusion in an infant presenting with primary refractory AMKL. In this NUP98r, the C-terminal chromatin recognition modules of BPTF, a core subunit of the NURF (nucleosome remodeling factor) ATP-dependent chromatin-remodeling complex, are fused to the N-terminal moiety of NUP98, creating an in frame NUP98-BPTF fusion, with structural homology to NUP98-KDM5A. The leukemic blasts expressed two NUP98-BPTF splicing variants, containing one or two tandemly spaced PHD chromatin reader domains. Our study also identified an unreported wild type BPTF splicing variant encoding for 2 PHD domains, detected both in normal cord blood CD34+ cells and in leukemic blasts, as with the fly BPTF homolog, Nurf301. Disease course was marked by rapid progression and primary chemoresistance, with ultimately significant tumor burden reduction following treatment with a clofarabine containing regimen. In sum, we report 2 novel NUP98-BPTF fusion isoforms that contribute to refine the NUP98r subgroup of pediatric AMKL. Multicenter clinical trials are critically required to determine the frequency of this fusion in AMKL patients and explore innovative treatment strategies for a disease still plagued with poor outcomes.


Assuntos
Antígenos Nucleares/genética , Leucemia Megacarioblástica Aguda/genética , Proteínas do Tecido Nervoso/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Fatores de Transcrição/genética , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Perfilação da Expressão Gênica , Humanos , Lactente , Cariotipagem , Leucemia Megacarioblástica Aguda/tratamento farmacológico , Masculino , Splicing de RNA
5.
Cancer Genet ; 235-236: 28-30, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31072725

RESUMO

Ewing sarcoma (ES), a common pediatric primary bone neoplasm, has a well-defined genomic landscape with various predisposing genomic elements including TP53, PMS2 and RET. Additionally, germline and somatic variants in protein tyrosine phosphatase delta (PTPRD), a tumor suppressor gene, have been identified in a limited number of ES patients. Here we present an ES patient, remarkable in terms of his young age and extent at presentation, found to have a PTPRD CNV. We explore the pathogenicity of this CNV, describe the patient's clinical course and touch upon the potential therapeutic implications in this subset of patients.


Assuntos
Neoplasias Ósseas/genética , Variações do Número de Cópias de DNA/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Sarcoma de Ewing/genética , Adolescente , Humanos , Masculino
6.
JAMA Psychiatry ; 75(5): 447-457, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29562078

RESUMO

Importance;: Copy number variants (CNVs) classified as pathogenic are identified in 10% to 15% of patients referred for neurodevelopmental disorders. However, their effect sizes on cognitive traits measured as a continuum remain mostly unknown because most of them are too rare to be studied individually using association studies. Objective: To measure and estimate the effect sizes of recurrent and nonrecurrent CNVs on IQ. Design, Setting, and Participants: This study identified all CNVs that were 50 kilobases (kb) or larger in 2 general population cohorts (the IMAGEN project and the Saguenay Youth Study) with measures of IQ. Linear regressions, including functional annotations of genes included in CNVs, were used to identify features to explain their association with IQ. Validation was performed using intraclass correlation that compared IQ estimated by the model with empirical data. Main Outcomes and Measures: Performance IQ (PIQ), verbal IQ (VIQ), and frequency of de novo CNV events. Results: The study included 2090 European adolescents from the IMAGEN study and 1983 children and parents from the Saguenay Youth Study. Of these, genotyping was performed on 1804 individuals from IMAGEN and 977 adolescents, 445 mothers, and 448 fathers (484 families) from the Saguenay Youth Study. We observed 4928 autosomal CNVs larger than 50 kb across both cohorts. For rare deletions, size, number of genes, and exons affect IQ, and each deleted gene is associated with a mean (SE) decrease in PIQ of 0.67 (0.19) points (P = 6 × 10-4); this is not so for rare duplications and frequent CNVs. Among 10 functional annotations, haploinsufficiency scores best explain the association of any deletions with PIQ with a mean (SE) decrease of 2.74 (0.68) points per unit of the probability of being loss-of-function intolerant (P = 8 × 10-5). Results are consistent across cohorts and unaffected by sensitivity analyses removing pathogenic CNVs. There is a 0.75 concordance (95% CI, 0.39-0.91) between the effect size on IQ estimated by our model and IQ loss calculated in previous studies of 15 recurrent CNVs. There is a close association between effect size on IQ and the frequency at which deletions occur de novo (odds ratio, 0.86; 95% CI, 0.84-0.87; P = 2.7 × 10-88). There is a 0.76 concordance (95% CI, 0.41-0.91) between de novo frequency estimated by the model and calculated using data from the DECIPHER database. Conclusions and Relevance: Models trained on nonpathogenic deletions in the general population reliably estimate the effect size of pathogenic deletions and suggest omnigenic associations of haploinsufficiency with IQ. This represents a new framework to study variants too rare to perform individual association studies and can help estimate the cognitive effect of undocumented deletions in the neurodevelopmental clinic.


Assuntos
Variações do Número de Cópias de DNA/genética , Inteligência/genética , Adolescente , Criança , Aberrações Cromossômicas , Estudos de Coortes , Europa (Continente) , Éxons , Feminino , Deleção de Genes , Triagem de Portadores Genéticos , Genótipo , Haploinsuficiência/genética , Humanos , Mutação com Perda de Função/genética , Masculino , Modelos Genéticos , Transtornos do Neurodesenvolvimento/genética , Quebeque , Estudos de Amostragem
7.
Sci Rep ; 6: 28663, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27363808

RESUMO

A challenge in clinical genomics is to predict whether copy number variation (CNV) affecting a gene or multiple genes will manifest as disease. Increasing recognition of gene dosage effects in neurodevelopmental disorders prompted us to develop a computational approach based on critical-exon (highly expressed in brain, highly conserved) examination for potential etiologic effects. Using a large CNV dataset, our updated analyses revealed significant (P < 1.64 × 10(-15)) enrichment of critical-exons within rare CNVs in cases compared to controls. Separately, we used a weighted gene co-expression network analysis (WGCNA) to construct an unbiased protein module from prenatal and adult tissues and found it significantly enriched for critical exons in prenatal (P < 1.15 × 10(-50), OR = 2.11) and adult (P < 6.03 × 10(-18), OR = 1.55) tissues. WGCNA yielded 1,206 proteins for which we prioritized the corresponding genes as likely to have a role in neurodevelopmental disorders. We compared the gene lists obtained from critical-exon and WGCNA analysis and found 438 candidate genes associated with CNVs annotated as pathogenic, or as variants of uncertain significance (VOUS), from among 10,619 developmental delay cases. We identified genes containing CNVs previously considered to be VOUS to be new candidate genes for neurodevelopmental disorders (GIT1, MVB12B and PPP1R9A) demonstrating the utility of this strategy to index the clinical effects of CNVs.


Assuntos
Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adulto , Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Criança , Deficiências do Desenvolvimento/metabolismo , Feminino , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Masculino , Proteômica/métodos
8.
BMC Med Genomics ; 7: 70, 2014 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-25539807

RESUMO

BACKGROUND: Molecular karyotyping is now the first-tier genetic test for patients affected with unexplained intellectual disability (ID) and/or multiple congenital anomalies (MCA), since it identifies a pathogenic copy number variation (CNV) in 10-14% of them. High-resolution microarrays combining molecular karyotyping and single nucleotide polymorphism (SNP) genotyping were recently introduced to the market. In addition to identifying CNVs, these platforms detect loss of heterozygosity (LOH), which can indicate the presence of a homozygous mutation or uniparental disomy. Since these abnormalities can be associated with ID and/or MCA, their detection is of particular interest for patients whose phenotype remains unexplained. However, the diagnostic yield obtained with these platforms is not confirmed, and the real clinical value of LOH detection has not been established. METHODS: We selected 21 children affected with ID, with or without congenital malformations, for whom standard genetic analyses failed to provide a diagnosis. We performed high-resolution SNP array analysis with four platforms (Affymetrix Genome-Wide Human SNP Array 6.0, Affymetrix Cytogenetics Whole-Genome 2.7 M array, Illumina HumanOmni1-Quad BeadChip, and Illumina HumanCytoSNP-12 DNA Analysis BeadChip) on whole-blood samples obtained from children and their parents to detect pathogenic CNVs and LOHs, and compared the results with those obtained on a moderate resolution array-based comparative genomic hybridization platform (NimbleGen CGX-12 Cytogenetics Array), already used in the clinical setting. RESULTS: We identified a total of four pathogenic CNVs in three patients, and all arrays successfully detected them. With the SNP arrays, we also identified a LOH containing a gene associated with a recessive disorder consistent with the patient's phenotype (i.e., an informative LOH) in four children (including two siblings). A homozygous mutation within the informative LOH was found in three of these patients. Therefore, we were able to increase the diagnostic yield from 14.3% to 28.6% as a result of the information provided by LOHs. CONCLUSIONS: This study shows the clinical usefulness of SNP arrays in children with ID, since they successfully detect pathogenic CNVs, identify informative LOHs that can lead to the diagnosis of a recessive disorder. It also highlights some challenges associated with the use of SNP arrays in a clinical laboratory.


Assuntos
Biomarcadores/metabolismo , Variações do Número de Cópias de DNA , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Genoma Humano , Perda de Heterozigosidade , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Criança , Pré-Escolar , Hibridização Genômica Comparativa/métodos , Feminino , Perfilação da Expressão Gênica , Humanos , Lactente , Cariotipagem , Masculino , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fenótipo
9.
J Neurodev Disord ; 6(1): 9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24834135

RESUMO

BACKGROUND: The chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking. METHODS: We conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder. RESULTS: Detailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene. CONCLUSIONS: The results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals.

11.
Hum Genet ; 120(2): 293-6, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16783568

RESUMO

The candidate gene for Mucopolysaccharidosis (MPS) type IIIC has been localized to the pericentric region of the chromosome 8 by the linkage disequilibrium analysis. To validate the localization of the gene, we rescued the deficient acetyl-coenzyme A: alpha-glucosaminide-N-acetylytransferase activity in the cultured cells of MPS IIIC patients by functional complementation via microcell-mediated chromosome transfer. The introduction of the target human monochromosome completely restored the activity confirming functional localization of the candidate gene on human chromosome 8.


Assuntos
Arilamina N-Acetiltransferase/genética , Cromossomos Humanos Par 8 , Fibroblastos/metabolismo , Mucopolissacaridose III/genética , Pele/citologia , Animais , Arilamina N-Acetiltransferase/deficiência , Fusão Celular , Linhagem Celular Tumoral , Células Cultivadas , Teste de Complementação Genética , Humanos , Células Híbridas , Ratos
12.
Am J Med Genet A ; 140(24): 2768-75, 2006 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-17103433

RESUMO

Cryptic unbalanced subtelomeric rearrangements have been identified as an important contributor ( approximately 6%) to the etiology of mental retardation and dysmorphism. Our objective was to study the role of these rearrangements in the development of fetal malformations. Multi-subtelomere FISH was performed on cells from 48 fetuses with major malformations diagnosed by prenatal ultrasound with a normal karyotype at a minimal 400 band resolution. We developed a method of performing multi-subtelomere FISH on a single slide of amniocyte metaphase spreads. We identified five subtelomeric abnormalities: two derivative chromosomes inherited from a parent carrying a balanced translocation, two known polymorphisms, and one novel familial variant. These results show a similar frequency (4%) of clinically significant subtelomeric rearrangements to that found in children with multiple malformations. This study adds to a growing number of reports of cryptic subtelomeric rearrangements associated with congenital malformations and highlights the relevance and technical feasibility of multi-subtelomere FISH screening of prenatal samples.


Assuntos
Aberrações Cromossômicas , Anormalidades Congênitas/genética , Hibridização in Situ Fluorescente/métodos , Diagnóstico Pré-Natal/métodos , Telômero/genética , Adulto , Amniocentese , Estudos de Coortes , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/diagnóstico por imagem , Feminino , Humanos , Masculino , Polimorfismo Genético , Gravidez , Ultrassonografia Pré-Natal
13.
Prenat Diagn ; 26(9): 810-3, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16821252

RESUMO

OBJECTIVES: To present a series of prenatally detected cases of recurrent pericentric inversions with euchromatic breakpoints and to review the literature to determine whether parental karyotyping is required for genetic counselling. METHODS: Cases of recurrent pericentric inversions with euchromatic breakpoints were collected from Canadian Cytogenetic Laboratories. Cases included inversions for chromosome 1(p13q21), chromosome 2(p11.2q13), chromosome 5(p13q13) and chromosome 10(p11.2q21.2). RESULTS: The incidence of de novo inv(2)(p11.2q13) was low, with one case among 91 inversions. There were no cases of de novo inv(10) (p11.2q21.2) among 17 reported and one case of de novo inv(5)(p13q13) among 21 reported. CONCLUSION: Our study, and data from the literature, suggests that most cases of inv(2)(p11.2q13) have been stably inherited, that de novo cases of inv(2) are rare and that both inherited and de novo forms are without phenotypic or developmental consequences. We suggest that parental karyotyping for cases of inv(2) is not useful in counselling as it may generate unnecessary parental anxiety over a chromosomal finding that is likely innocuous.


Assuntos
Transtornos Cromossômicos/diagnóstico , Inversão Cromossômica/genética , Cromossomos Humanos Par 2/genética , Pai , Aconselhamento Genético , Mães , Diagnóstico Pré-Natal/métodos , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 5 , Feminino , Humanos , Cariotipagem , Gravidez , Risco
14.
Am J Med Genet A ; 135(3): 317-9, 2005 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-15887259

RESUMO

We report on the diagnosis of a complex chromosome rearrangement in a mother and the transmission of a simplified translocation in her fetus. The mother had mental retardation, short stature, facial dysmorphism, and hydronephrosis, but was never investigated before she was pregnant. A blood sample was taken for karyotyping at the time of amniocentesis for advanced maternal age. The mother's karyotype revealed two translocations involving chromosome 5, chromosome 16 twice, and chromosome 20 as follow: 46,XX,t(5;16;20)(5pter-->5q11.2::16q12.1-->16q23::20p11.2-->20pter;16pter-->16q12.1::5q11.2-->5qter;16qter-->16q23::20p11.2-->20qter). The amniocentesis revealed a female karyotype with an apparently balanced translocation: 46,XX,t(16;20)(q23;p11.2). The translocation of the fetus probably resulted from a meiotic recombination between the derived 5 and the normal 16 in the mother. The baby was born and presented the same facial dysmorphism and hydronephrosis. The simplification of a complex rearrangement through recombination into a balanced product has only been rarely described and it is to our knowledge the first time that both the carrier of the complex rearrangement and her descendant with a simplified rearrangement share phenotypic abnormalities.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/genética , Translocação Genética/genética , Adulto , Amniocentese , Bandeamento Cromossômico , Transtornos Cromossômicos/patologia , Coloração Cromossômica , Feminino , Humanos , Lactente , Cariotipagem , Idade Materna , Modelos Genéticos , Mães , Núcleo Familiar , Fenótipo , Gravidez
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