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1.
Cytogenet Genome Res ; 158(4): 192-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31394532

RESUMO

Prader-Willi syndrome (PWS) and recurrent 15q13.3 microdeletion syndrome can be caused by genomic rearrangements in the complex 15q11q13 chromosomal region. Here, we describe the first female child with PWS and 15q13.3 microdeletion syndrome resulting from an unusual 10.7-Mb deletion from 15pter to 15q13.3 due to an unbalanced de novo 15;19 translocation. The patient presents with hypotonia, microcephaly, developmental delay with lack of speech, intellectual disability, happy demeanor, clinodactyly of the 4th and 5th fingers, and dysmorphic facial features discordant for PWS and consistent with an atypical phenotype.


Assuntos
Transtornos Cromossômicos/complicações , Transtornos Cromossômicos/genética , Deficiência Intelectual/complicações , Deficiência Intelectual/genética , Síndrome de Prader-Willi/complicações , Síndrome de Prader-Willi/genética , Convulsões/complicações , Convulsões/genética , Translocação Genética/genética , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 15/genética , Feminino , Humanos , Recém-Nascido
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 672-675, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302908

RESUMO

OBJECTIVE: To explore the genetic basis for three patients with development delay and to correlate their clinical phenotypes with genetic findings. METHODS: The karyotypes of the probands and their parents were analyzed by conventional G-banding. Chromosomal microarray analysis (CMA) was used to detect microdeletion and microduplication. RESULTS: No kartotypic abnormality was detected in the patients and their parents. CMA analysis identified a de novo 3.10 Mb deletion on chromosome 15q24.1q24.2 in case 1, a de novo 3.14 Mb deletion at 15q24.1q24.2 in case 2, and a 3.13 Mb deletion at 15q24.1q24.2 in case 3. All deletions have encompassed the CPLX3,SEMA7A and SIN3A genes. CONCLUSION: The three patients were diagnosed with 15q24 microdeletion syndrome. CPLX3,SEMA7A and SIN3A may be the key genes responsible for this syndrome.


Assuntos
Transtornos Cromossômicos/genética , Deficiência Intelectual/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Antígenos CD/genética , Criança , Deleção Cromossômica , Cromossomos Humanos Par 15/genética , Proteínas Ligadas por GPI/genética , Humanos , Proteínas Repressoras/genética , Semaforinas/genética
3.
Cytogenet Genome Res ; 158(2): 63-73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31261151

RESUMO

Terminal deletion of chromosome 4 (4q deletion syndrome) is a rare genetic condition that is characterized by a broad clinical spectrum and phenotypic variability. Diagnosis of the distinct condition can be identified by conventional chromosome analysis and small deletions by novel molecular cytogenetic methods such as microarray comparative genome hybridization (aCGH). Prenatal diagnosis is challenging; to date 10 cases have been described. We report a prenatally diagnosed case of de novo 4q deletion syndrome confirmed by conventional karyotyping and FISH due to an elevated combined risk for Down syndrome and prenatal ultrasound findings. aCGH validated the diagnosis and offered exact characterization of the disorder. Cytogenetic and microarray results described a 4q32.1qter terminal deletion of the fetus. Prenatal ultrasound detected multiple nonstructural findings (micrognathia, choroid plexus cysts, echogenic fetal bowel, short femur, and cardiac axis deviation). Pregnancy was terminated at 20 weeks. In addition to the index patient, we reviewed the 10 prenatally published cases of 4q deletion syndrome in the literature and compared these with our results. We summarize the patients' characteristics and prenatal clinical findings. Alterations of maternal serum biochemical factors, an elevated combined risk for trisomies, and distinct ultrasonographic findings can often be observed in cases of prenatal 4q deletion syndrome and may facilitate the otherwise difficult prenatal diagnosis.


Assuntos
Transtornos Cromossômicos/diagnóstico , Hibridização in Situ Fluorescente/métodos , Cariotipagem/métodos , Diagnóstico Pré-Natal/métodos , Aborto Induzido , Adulto , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 4/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Idade Materna , Fenótipo , Gravidez , Fatores de Risco
4.
Hum Genet ; 138(10): 1145-1153, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321490

RESUMO

The objective of this study is to shed light on the phenotype and inheritance pattern of rare 13q33-q34 microdeletions. Appropriate cases were retrieved using local databases of two largest Israeli centers performing CMA analysis. In addition, literature search in PubMed, DECIPHER and ClinVar databases was performed. Local database search yielded eight new patients with 13q33.1-q34 microdeletions (three of which had additional copy number variants). Combined with 15 cases detected by literature search, an additional 23 cases were reported in DECIPHER database, and 17 cases from ClinVar, so overall 60 patients with isolated 13q33.1-q34 microdeletions were described. Developmental delay and/or intellectual disability were noted in the vast majority of affected individuals (81.7% = 49/60). Of the 23 deletions involving the 13q34 cytoband only, in 3 cases, developmental delay and/or intellectual disability was not reported. Interestingly, in two of these cases (66.7%), the deletions did not involve the terminal CHAMP1 gene, as opposed to 3/20 (15%) of patients with 13q34 deletions and neurocognitive disability. Facial dysmorphism and microcephaly were reported in about half of the overall cases, convulsions were noted in one-fifth of the patients, while heart anomalies, short stature and hypotonia each involved about 10-30% of the cases. None of the 13q33-q34 deletions were inherited from a reported healthy parent. 13q33-q34 microdeletions are rare chromosomal aberrations, associated with high risk for neurodevelopmental disability. The rarity of this chromosomal aberration necessitates continuous reporting and collection of available evidence, to improve the ability to provide accurate genetic counseling, especially in the context of prenatal setting.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13 , Fenótipo , Adolescente , Adulto , Criança , Pré-Escolar , Bandeamento Cromossômico , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Feminino , Humanos , Lactente , Recém-Nascido , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Adulto Jovem
5.
J Clin Pediatr Dent ; 43(4): 288-291, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31094634

RESUMO

The 13q deletion syndrome is a rare genetic disorder caused by structural and functional monosomy of chromosome 13. On 13q34, which is the terminal of the long arm, causative genes of coagulation factors VII and X (FVII and FX) are mapped. Patients with a combination of FVII and FX deficiencies are extremely rare and there have been few articles about perioperative coagulation support for such patients. Herein, we report on a case of bilateral cleft lip and palate accompanied by 13q deletion syndrome with deficiencies of FVII and FX. The chromosomal investigation indicated 46, XX, del(13)(q33) by G-banding. Prothrombin time and activated partial thromboplastin time were found to be 21.0 seconds (sec) (prothrombin time-international normalized ratio 1.76) and 41.6 sec (normal range; 23.9 - 39.7 sec), respectively. The activities of coagulation FVII and FX were 22% and 36%, respectively. A two-stage cheiloplasty was performed at 4 and 7 months of age followed by a palatoplasty at 1 year and 6 months. Tranexamic acid was given intravenously three times a day for three days after each surgery. There were no adverse events such as bleeding from the oral or nasal cavities and healing of the surgical wound was good without dehiscence.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos , Cromossomos Humanos Par 13 , Fenda Labial , Fissura Palatina , Deficiência do Fator VII , Transtornos Cromossômicos/complicações , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Fenda Labial/genética , Fissura Palatina/genética , Fator VII , Deficiência do Fator VII/genética , Humanos , Palato
7.
J Genet ; 982019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945666

RESUMO

The aim of the present study was to evaluate the diagnostic yield of prenatal cytogenetic microarray (CMA) in structurally normal and abnormal foetuses and record the acceptance rate of CMA for prenatal diagnosis over a course of five year. In 128 structurally normal and abnormal foetuses, CMA was performed along with foetal karyotype, after exclusion of aneuploidy by quantitative fluorescence polymerase chain reaction. The microarray was able to detect the pathogenic variants in 5.5% cases; the diagnostic yield in structurally abnormal foetuses was 8.8% and 4.7% in foetuses with a high aneuploidy risk. Balanced and unbalanced translocations, and low level mosaicism were detected. Reanalysis of variants of uncertain significance identified pathogenic variant. The study shows higher diagnostic yield in structurally abnormal cases, the importance of foetal karyotype and reanalysis in microarray. The acceptance rate of prenatal CMA increased five-fold over a period of five year.


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/genética , Análise Citogenética/métodos , Doenças Fetais/genética , Testes Genéticos/normas , Análise em Microsséries/métodos , Diagnóstico Pré-Natal/métodos , Cariótipo Anormal , Adulto , Transtornos Cromossômicos/diagnóstico , Feminino , Doenças Fetais/diagnóstico , Humanos , Gravidez , Prognóstico
8.
Mol Genet Genomic Med ; 7(3): e545, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30706702

RESUMO

BACKGROUND: We evaluated the performance of a cell-free DNA (cfDNA) prenatal screening assay for trisomies 21, 18, and 13, and sex chromosome aneuploidies (SCAs) among a population of pregnant women that included both those at average and high risk. METHODS: Specimen collection, cfDNA extraction, massively parallel sequencing, and bioinformatics analysis were conducted per laboratory protocol. Assay results, concordance with pregnancy outcomes, and performance characteristics were evaluated. RESULTS: A total 75,658 specimens from 72,176 individual pregnant women were received. Technical reasons accounted for 288 (0.4% of all received samples) tests not performed. In the final analysis cohort (N = 69,794), 13% of pregnancies were considered at average risk and 87% at high risk. Mean gestational age at specimen collection was 15.1 weeks. Of the 69,794 unique pregnancies, 1,359 (1.9%) had positive test results. Among the results with confirmed outcomes, PPV for trisomies 21, 18, and 13 was 98.1%, 88.2%, and 59.3%, respectively; the PPV was 69.0% for SCAs and 75.0% for microdeletions. Overall, PPV was 87.2%, sensitivity was 97.9%, and specificity was 99.9%. CONCLUSION: This cfDNA prenatal screening assay provides highly accurate discrimination between affected and unaffected pregnancies among a population of pregnant women at average and high risk for fetal genetic abnormalities.


Assuntos
Aneuploidia , Ácidos Nucleicos Livres/genética , Transtornos Cromossômicos/diagnóstico , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Ácidos Nucleicos Livres/química , Transtornos Cromossômicos/genética , Feminino , Testes Genéticos/normas , Humanos , Gravidez , Diagnóstico Pré-Natal/normas , Reprodutibilidade dos Testes , Análise de Sequência de DNA/métodos , Análise de Sequência de DNA/normas
9.
J Assist Reprod Genet ; 36(4): 749-757, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30739229

RESUMO

PURPOSE: To clarify the associations of the maternal age, history of miscarriage, and embryonic/fetal size at miscarriage with the frequencies and profiles of cytogenetic abnormalities detected in spontaneous early miscarriages. METHODS: Miscarriages before 12 weeks of gestation, whose karyotypes were evaluated by G-banding between May 1, 2005, and May 31, 2017, were included in this study. The relationships between their karyotypes and clinical findings were assessed using trend or chi-square/Fisher's exact tests and multivariate logistic analyses. RESULTS: Three hundred of 364 miscarriage specimens (82.4%) had abnormal karyotypes. An older maternal age was significantly associated with the frequency of abnormal karyotype (ptrend < 0.001), particularly autosomal non-viable and viable trisomies (ptrend 0.001 and 0.025, respectively). Women with ≥ 2 previous miscarriages had a significantly lower possibility of miscarriages with abnormal karyotype than women with < 2 previous miscarriages (adjusted odds ratio [aOR], 0.48; 95% confidence interval [95% CI], 0.27-0.85). Although viable trisomy was observed more frequently in proportion to the increase in embryonic/fetal size at miscarriage (ptrend < 0.001), non-viable trisomy was observed more frequently in miscarriages with an embryonic/fetal size < 10 mm (aOR, 2.41; 95% CI, 1.27-4.58), but less frequently in miscarriages with an embryonic/fetal size ≥ 20 mm (aOR, 0.01; 95% CI, 0.00-0.07) than in anembryonic miscarriages. CONCLUSIONS: The maternal age, history of miscarriage, and embryonic/fetal size at miscarriage may be independently associated with the frequencies or profiles of cytogenetic abnormalities in early miscarriages.


Assuntos
Feto Abortado/patologia , Aborto Espontâneo/genética , Citogenética , Trissomia/genética , Cariótipo Anormal , Aborto Espontâneo/patologia , Adulto , Aneuploidia , Vilosidades Coriônicas/patologia , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/patologia , Feminino , Feto/patologia , Humanos , Cariótipo , Cariotipagem , Idade Materna , Mosaicismo , Gravidez , Estudos Retrospectivos , Trissomia/patologia
10.
Zhonghua Fu Chan Ke Za Zhi ; 54(2): 87-92, 2019 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-30803166

RESUMO

Objective: To analyze the clinical characteristics of structural malformations in one of monochorionic diamnionic twins (MCDA). Methods: The clinical data of 77 MCDA patients with structural malformations diagnosed by ultrasound were retrospectively reviewed from January 2012 to May 2017. The distribution of structural malformations, prenatal chromosomal karyotyping and pregnancy outcomes were analyzed. Results: (1)Among the 77 MCDA patients with structural malformations, the single malformation accounted for 79%(61/77), the multiple malformations accounted for 21%(16/77). And there were a total of 94 types of malformations, the top three malformations were neurological malformations (32%, 30/94), cardiovascular malformations (29%, 27/94) and twin reversed arterial perfusion sequence (TRAPS;10%,9/94).(2)Among the 77 patients with structural malformation, 64 cases (83%, 64/77) were examined for fetal chromosomes, of whom 14 cases (22%,14/64) were examined for fetal chromosomes of both twins, with 1 case (1/14) of discordant fetal chromosome. (3)Among the 77 patients, 4 cases (5%, 4/77) with severe fetal malformations terminated pregnancy. Totally 29 cases (38%,29/77) with severe malformations were treated with selective fetal reduction, among whom 7 cases (24%, 7/29) experienced unexplained fetal death within 24 hours after the operation; 2 cases (7%, 2/29) happened inevitable abortion, and 2 cases (7%, 2/29) underwent unexplained fetal death during the late pregnancy. Of the remaining 44 patients (57%,44/77) with expectant treatment, 13 cases (30%,13/44) occurred twin transfusion syndrome (Ⅱ-Ⅳ), and were treated with fetoscopic laser occlusion. Eight patients had 2 survival twins, 4 patients delivered 1 survival twin, and 1 patient had dead twins. Conclusions: The most common malformations in MCDA twins are the nervous malformations, cardiovascular malformations and TRAPS. The chromosome karyotype of MCDA twins with structural malformations are sometimes discordant, and separate samling of the twins is suggested for prenatal diagnosis. Selective fetal reduction could be given to severe structural malformation in MCDA patients safely and effectively. For non-severe structural malformation in MCDA patients with twin transfusion syndrome, fetoscopic laser occlusion is safe and effective.


Assuntos
Transtornos Cromossômicos/genética , Anormalidades Congênitas/genética , Doenças em Gêmeos/genética , Transfusão Feto-Fetal , Gravidez de Gêmeos , Gêmeos Monozigóticos/genética , Gêmeos/genética , Transtornos Cromossômicos/diagnóstico , Doenças em Gêmeos/diagnóstico , Feminino , Fetoscopia , Humanos , Cariotipagem , Gravidez , Gravidez de Gêmeos/genética , Gravidez de Gêmeos/fisiologia , Gravidez de Gêmeos/estatística & dados numéricos , Diagnóstico Pré-Natal , Estudos Retrospectivos , Ultrassonografia Pré-Natal
11.
Mol Genet Genomic Med ; 7(4): e00597, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30767419

RESUMO

BACKGROUND: The noninvasive prenatal testing (NIPT) has been successfully used in the clinical screening of fetal trisomy 13, 18, and 21 in the last few years and researches on detecting sub-chromosomal copy number variations (CNVs) and monogenic diseases are also in progress. To date, multiple tests are needed in order to complete a full set of fetus disorder screening, which is costly and time consuming. Therefore, an integrated 3-in-1 NIPT approach will be in great demand by routine clinical practice in the near future. METHODS: We designed a target capture sequencing panel with an associate bioinformatics pipeline to create a novel multi-functional NIPT method and we evaluated its performance by testing 22 clinical samples containing aneuploidy, CNV, and single-gene disorder. Chromosomal aneuploidy and CNV were detected based on the Z-value approach, whereas single-gene disorder was identified by using the "pseudo-tetraploid" model to estimate the best-suited genotype for each locus. RESULTS: The performance of this newly constructed 3-in-1 system was promising. We achieved a 100% detection rate for chromosomal aneuploidies (7/7), a 100% diagnosis rate for fetus CNVs larger than 20 Mb (3/3), and an 86.4% accuracy for single-gene disorder screening (19/22). CONCLUSION: For the first time, we showed that it is possible to use just a single NIPT test to detect three distinct types of fetus disorder and laid a foundation for developing a cheaper, faster, and multi-functional NIPT method in the future.


Assuntos
Aneuploidia , Variações do Número de Cópias de DNA , Testes Genéticos/métodos , Mutação , Diagnóstico Pré-Natal/métodos , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Feminino , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Testes Genéticos/normas , Humanos , Projetos Piloto , Gravidez , Diagnóstico Pré-Natal/normas , Sensibilidade e Especificidade , Análise de Sequência de DNA/métodos , Análise de Sequência de DNA/normas
12.
PLoS Genet ; 15(1): e1007879, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30653500

RESUMO

Variably expressive copy-number variants (CNVs) are characterized by extensive phenotypic heterogeneity of neuropsychiatric phenotypes. Approaches to identify single causative genes for these phenotypes within each CNV have not been successful. Here, we posit using multiple lines of evidence, including pathogenicity metrics, functional assays of model organisms, and gene expression data, that multiple genes within each CNV region are likely responsible for the observed phenotypes. We propose that candidate genes within each region likely interact with each other through shared pathways to modulate the individual gene phenotypes, emphasizing the genetic complexity of CNV-associated neuropsychiatric features.


Assuntos
Variações do Número de Cópias de DNA/genética , Estudos de Associação Genética , Heterogeneidade Genética , Predisposição Genética para Doença , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/fisiopatologia , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/fisiopatologia , Duplicação Cromossômica/genética , Regulação da Expressão Gênica , Humanos , Fenótipo , Síndrome de Smith-Magenis/genética , Síndrome de Smith-Magenis/fisiopatologia , Síndrome de Sotos/genética , Síndrome de Sotos/fisiopatologia , Síndrome de Williams/genética , Síndrome de Williams/fisiopatologia
13.
Asian Pac J Cancer Prev ; 20(1): 235-241, 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30678438

RESUMO

Objective: Multiple myeloma (MM) is a clinically and genetically heterogeneous plasma cell neoplasm. The prognosis of MM patients is dependent on several factors including the patient's age, the stage of disease and genetic alterations. This study aimed to determine the frequency of common chromosomal abnormalities and their significance in MM patients referred to a tertiary healthcare center in India. Methods: Fluorescence in situ hybridization on interphase nuclei from bone marrow cells using seven MM-specific probes for recurrent aberrations was performed in a total of 215 newly diagnosed patients. Results: Chromosomal abnormalities were detected in 161 (74.9%) MM patients in this study. The most frequent aberration was trisomy(ies) involving only gain of chromosomes in 48 (22.3%) cases. A translocation involving the IGH gene alone or accompanied by trisomy(ies) or by monosomy 13/13q deletion or by both was registered in 80 (37.2%) patients. Atypical patterns such as a deletion of the IGH variable segment (IGHv) on the derivative chromosome 14 or on the native (normal) chromosome 14, biallelic deletion of IGHv, deletion of the IGH constant segment on the rearranged chromosome14 and extra fusions were noticed in 21 (9.8%) patients with an IGH rearrangement. Monosomy 13/deletion 13q was identified singly or as part of a complex karyotype in 74 patients (34.4%). Clonal heterogeneity and additional abnormalities including TP53 deletion and monosomies of chromosomes 4, 9, 14 and 16 were recorded in 18.6% and 16.3% of patients respectively. Patients with abnormalities exhibited plasmacytosis, reduced hemoglobin value and high level of ß2-microglobulin. Conclusions: A lower median age and a low frequency of IGH translocations particularly t(11;14) and chromosome 13 abnormalities suggest ethnic diversity. Further investigations on genetic alterations including IGH deletions will contribute to improved insights into the biology of myeloma disease, risk stratification and patient management.


Assuntos
Cromossomos/genética , Mieloma Múltiplo/genética , Idoso , Aberrações Cromossômicas , Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Feminino , Humanos , Índia , Cariotipagem/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Atenção Terciária à Saúde/métodos , Translocação Genética/genética
14.
Stem Cell Res ; 34: 101377, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616144

RESUMO

Skin fibroblasts from a patient with developmental delay and chromosome 2p25.3 deletion syndrome were reprogrammed into induced pluripotent stem cells (iPSCs) and the clonal stem cell line ICAGi001-A (iTAF9-11) was established. ICAGi001-A pluripotency was demonstrated in vitro by three germ layer differentiation capacity. This line is a good model for studying of the developmental delay and brain disorder.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 2/genética , Fibroblastos/patologia , Células-Tronco Pluripotentes Induzidas/patologia , Pele/patologia , Linhagem Celular , Pré-Escolar , Feminino , Humanos
15.
Brain Dev ; 41(5): 452-455, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30635136

RESUMO

1q41q42 microdeletion syndrome has been established in 2007. Since then, more than 17 patients have been reported so far. The reported deletions showed random breakpoints and deletion regions are aligned as roof tiles. Patients with 1q41q42 microdeletion syndrome show intellectual disability, seizures, and distinctive features. Many genotype-phenotype correlation studies have been performed and some genes included in this region have been suggested as potential candidate genes. Recently, de novo variants in WDR26 and FBXO28 were identified in patients who showed consistent phenotypes with 1q41q42 microdeletion syndrome. Thus, both genes are now considered as the genes possibly responsible for 1q41q42 microdeletion syndrome. Here, the first case of a Japanese patient with a de novo 1q41q42 microdeletion is reported. Owing to the distinctive features, this syndrome would be clinically recognizable.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/fisiopatologia , Cromossomos Humanos Par 1/genética , Transtornos Neurológicos da Marcha/genética , Deficiência Intelectual/genética , Proteínas/genética , Proteínas Ligases SKP Culina F-Box/genética , Criança , Feminino , Humanos , Japão , Fenótipo , Síndrome
17.
Neonatal Netw ; 37(5): 303-309, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30567812

RESUMO

Chromosome 16p13.11 microdeletion syndrome is a rare copy number variant that carries increased risks for complications in the neonatal period and throughout the life span. Clinical manifestations and associated defects known to present in the neonatal period include motor delay, facial dysmorphisms, microcephaly, gastroesophageal reflux disease (GERD), and congenital heart defects. Management in the neonatal period focuses on associated comorbidities, including motor delay with or without GERD, which commonly manifests as feeding difficulties. Life span implications of chromosome 16p13.11 microdeletion syndrome include developmental, speech, and language delay; psychiatric and behavioral problems; seizure disorders; and, less commonly, obesity. Nursing assessment is critical to the early identification of nonspecific abnormalities associated with de novo genetic disorders. Early identification and diagnosis of chromosome 16p13.11 microdeletion syndrome are critical to optimizing outcomes throughout infancy and across the life span. We present a case report of an infant diagnosed with chromosome 16p13.11 microdeletion. A discussion of genetic influences, associated clinical manifestations, diagnostics, management, and health promotion strategies are presented to establish core knowledge of chromosome 16p13.11 microdeletion.


Assuntos
Deleção Cromossômica , Transtornos Cromossômicos/genética , Transtornos Cromossômicos/enfermagem , Cromossomos Humanos Par 16 , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/enfermagem , Enfermagem Neonatal/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Resultado do Tratamento
18.
Zhonghua Fu Chan Ke Za Zhi ; 53(7): 464-470, 2018 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-30078256

RESUMO

Objective: To investigate the value of single nucleotide polymorphism array (SNP-array) for fetuses with abnormal ultrasound findings. Method: A total of 904 fetuses with abnormal ultrasound findings were enrolled in this study from May 2015 to November 2017, and 434 (48.0%) cases received conventional karyotyping analysis at the same time. According to different abnormal ultrasound category, 904 cases were divided into 5 groups: 280 cases (31.0%) in single system structural anomalies, 31 cases (3.4%) in multiple system structural anomalies, 331 cases (36.6%) in single ultrasound soft marker abnormalities without structural anomalies, 107 cases (11.8%) in multiple soft marker abnormalities and 155 cases (17.2%) in structural abnormalities combined with soft markers abnormalities. Abnormal detection rates by SNP-array among 5 groups of abnormal ultrasound category were calculated. Result: (1) Total SNP-array results: 171 (19.0%) cases out of 904 cases analyzed by SNP-array, presented chromosomal abnormalities. Pathogenic copy number variants were detected in 27 cases (3.0%) and variants of unknown significance were detected in 81 cases (7.8%) . In addition, 7 cases (26.0%) were found with new mutation by parental validation. (2) SNP-array of 5 groups: among the 5 groups of abnormal ultrasound category, chromosomal abnormalities were identified by SNP-array in 19.3% (54/280) with single system structural abnormalities, 25.8% (8/31) with multiple system structural abnormalities, 13.9% (46/331) with single nonstructural anomalies, 19.6% (21/107) with multiple nonstructural anomalies and 27.1% (42/155) with structural abnormalities combined with nonstructural anomalies. The differences were significant (P=0.010) . No chromosome abnormalities was identified in single soft marker abnormalities, such as choroid plexus cysts, echogenic foci in the heart, single umbilical artery and pyelectasis. (3) Chromosomal abnormalities: the abnormal detection rate of aneuploidy chromosomal abnormalities by SNP-array increased with the maternal age, decreased with the gestational weeks (all P<0.05) . However, the pathogenic copy number variants and variants of unknown significance rates did not change with maternal age and gestational weeks (all P>0.05) . (4) SNP-array and karyotyping: 434 cases were analyzed by conventional karyotyping and SNP-array respectively, 10.3% (43/419) of which presented chromosomal abnormalities by conventional karyotyping and 18.7% (81/434) of which presented chromosomal abnormalities by SNP-array. Conclusions: SNP-array could be a useful genetic analysis method in prenatal diagnosis for fetuses with abnormal ultrasound findings. For different abnormal ultrasound category, SNP-array has different detection rate. Compared with conventional karyotyping analysis, SNP-array can improve the detection rates for chromosomal abnormalities and find the chromosome abnormalities which can't be detected by conventional karyotyping analysis. In clinical prenatal genetic counseling, SNP-array should be selected rationally in combination with the various abnormal ultrasound category.


Assuntos
Anormalidades Múltiplas/genética , Transtornos Cromossômicos/genética , Anormalidades Congênitas/genética , Variações do Número de Cópias de DNA , Cariotipagem/métodos , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Natal/métodos , Ultrassonografia Pré-Natal/métodos , Anormalidades Múltiplas/diagnóstico por imagem , Aneuploidia , Aberrações Cromossômicas , Anormalidades Congênitas/diagnóstico por imagem , Feminino , Feto , Aconselhamento Genético , Testes Genéticos , Humanos , Idade Materna , Gravidez
19.
Medicine (Baltimore) ; 97(34): e12057, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30142861

RESUMO

The aim of this study was to investigate the value of chromosomal microarray analysis (CMA) for the prenatal diagnosis of orofacial clefts.A total of 143 fetuses with oral clefts were detected by ultrasound during prenatal exam between 2012 and 2017 in our center. We categorized the cases into 4 groups: isolated cleft lip (CL) (CL only), isolated cleft palate (CP only), isolated cleft lip and palate (CLP) (CLP only), and syndromic CLP (combined with other malformations). The CMA was performed in all cases, while 139 fetuses were referred for G-banded chromosome analysis.There were 42 male and 10 female fetuses were born, with a sex ratio of 4.2:1. The isolated CLP group accounted for 74.1% (106/143) of cases, while the isolated CL, isolated CP, and syndromic CP groups accounted for 13.9% (20/143), 2% (3/143), and 10% (14/143), respectively. A total of 11 fetuses had pathogenic copy number variants (CNVs, 7.7%), including isolated CP (1/143, 0.7%), isolated CLP (5/143, 3.5%), and syndromic CLP (5/143, 3.5%). Compared with the CMA results, 5 fetuses were found to have an abnormal karyotype (5/139, 3.6%). However, no abnormalities were found in either karyotype analysis or CMA in the isolated CL group.CMA is a valuable tool for identifying submicroscopic chromosomal abnormalities in the prenatal diagnosis of oral clefts. An excellent outcome can be expected for fetuses with isolated CL that are negative for chromosomal abnormalities.


Assuntos
Transtornos Cromossômicos/diagnóstico , Fenda Labial/diagnóstico , Fissura Palatina/diagnóstico , Análise em Microsséries/métodos , China , Aberrações Cromossômicas , Transtornos Cromossômicos/genética , Fenda Labial/genética , Fissura Palatina/genética , Variações do Número de Cópias de DNA , Feminino , Feto , Humanos , Recém-Nascido , Cariotipagem , Masculino , Gravidez , Diagnóstico Pré-Natal
20.
Nanotechnology ; 29(43): 434001, 2018 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-30087212

RESUMO

Non-invasive prenatal diagnostics (NIPD) has been an emerging field for prenatal diagnosis research. Carrying the whole genome coding of the fetus, fetal nucleated red blood cells (FNRBCs) have been pursued as a surrogate biomarker traveling around in maternal blood. Here, by combining a unique microbead-based centrifugal separation and enzymatic release, we demonstrated a novel method for FNRBC isolation from the blood samples. First, the gelatin-coated silica microbeads were modified with FNRBC-specific antibody (anti-CD147) to capture the target cells in the blood samples. Then, the density difference between microbead-bound FNRBCs and normal blood cells enables the purification of FNRBCs via an improved high-density percoll-based separation. The non-invasive release of FNRBCs can then be achieved by enzymatically degrading the gelatin film on the surface of the microbeads, allowing a gentle release of the captured target cells with as high as 84% efficiency and ∼80% purity. We further applied it to isolate fetal cells from maternal peripheral blood. The released cells were analyzed by real-time polymerase chain reaction to verify their fetal origin and fluorescent in situ hybridization to detect fetal chromosome disorders. This straightforward and reliable alternative platform for FNRBC detection may have the potential for realizing facile NIPD.


Assuntos
Separação Celular/métodos , Eritrócitos/citologia , Feto/citologia , Diagnóstico Pré-Natal/métodos , Anticorpos Imobilizados/química , Basigina/análise , Separação Celular/economia , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Eritrócitos/metabolismo , Feminino , Feto/metabolismo , Humanos , Hibridização in Situ Fluorescente , Microesferas , Gravidez , Diagnóstico Pré-Natal/economia
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