RESUMO
OBJECTIVE: To explore the genetic characteristics of a fetus with sex chromosome abnormality indicated by non-invasive prenatal testing (NIPT) at 25+ gestational weeks. METHODS: A pregnant woman who was admitted to the Taizhou Hospital for abnormal NIPT result on January 6, 2023 was selected as the study subject. Relevant clinical data was collected. The fetus was subjected to chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), fluorescence in situ hybridization (FISH), and multiplex PCR assays. RESULTS: NIPT had suggested monosomy of X chromosome. The fetus was found to have a chromosomal karyotype of 45,X[59]/46,X,del(Y)(q11.2)[17] at 30+ weeks of gestational age. CNV-seq suggested the presence a 7.98 Mb deletion at Yq11.222q12 and a mosaicism 16.92 Mb deletion. FISH suggested that the fetus harbored two SRY genes and a mosaicism sex chromosomal abnormality, and multiplex PCR revealed that its AZF b+c region was completely deleted. C-banded karyotyping showed darkly stained dense mitotic granules at both ends of the Y chromosome. The fetus was ultimately determined as a 45,X/46,X,idic(Y)(q11.2) mosaicism. Following elected abortion, testing of the fetal tissue confirmed the presence of 45,X/46,XY mosaicism, and CNV-seq result of the placental tissue was compatible with that of NIPT. CNV-seq analysis of the couple revealed no obvious abnormality. CONCLUSION: With combined NIPT, karyotyping, CNV-seq, FISH and multiplex PCR assays, the fetus was diagnosed as a 45,X/46,X,idic(Y)(q11.2) mosaicism with deletion of the AZF b+c region. Above finding has enabled prenatal diagnosis for the fetus.
Assuntos
Cromossomos Humanos X , Hibridização in Situ Fluorescente , Cariotipagem , Mosaicismo , Aberrações dos Cromossomos Sexuais , Humanos , Mosaicismo/embriologia , Feminino , Gravidez , Cromossomos Humanos X/genética , Adulto , Aberrações dos Cromossomos Sexuais/embriologia , Diagnóstico Pré-Natal , Feto , Variações do Número de Cópias de DNA , Cromossomos Humanos Y/genética , Masculino , Testes Genéticos/métodosRESUMO
OBJECTIVE: We present mosaic Xq duplication, or 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)/46,XX at amniocentesis in a pregnancy with a favorable outcome. CASE REPORT: A 40-year-old woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a result of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[7]/46,XX[20]. Simultaneous array comparative genomic hybridization (aCGH) analysis on the DNA extracted from uncultured amniocytes revealed the result of arr (1-22, X) × 2. Cytogenetic analysis on maternal blood revealed a karyotype of 46,XX. At 22 weeks of gestation, she underwent repeat amniocentesis which revealed a karyotype of 46,XX in 22/22 colonies of cultured amniocytes and an aCGH result of (1-22, X) × 2 in the uncultured amniocytes. Prenatal ultrasound findings were unremarkable. The parents decided to continue the pregnancy, and a healthy female baby was delivered at 39 weeks of gestation with a body weight of 3510 g and a body length of 49 cm. The cord blood had a karyotype of 46,X,der(X)dup(X)(q22.1q22.2)dup(X)(q25q22.3)[3]/46,XX[37]. At age two months, interphase fluorescence in situ hybridization (FISH) analysis on buccal mucosal cells showed Xq duplication signals in 1.25% (1/80 cells), compared with 0% (0/90 cells) in the normal control. At age nine months, the neonate had normal physical and psychomotor development. Her body weight was 9.6 Kg (85th - 97th centile), and body length was 72 cm (50th - 85th centile). Cytogenetic analysis of peripheral blood revealed a karyotype of 46,X,der(X)dup(X) (q22.1q22.2)dup(X)(q25q22.3)[1]/46,XX[39]. Interphase FISH analysis on 100 buccal mucosal cells revealed no abnormal signal. CONCLUSION: In case of mosaicism for an Xq duplication with a normal euploid cell line at amniocentesis, the in-vitro culture process of amniocytes may cause over-estimation of the mosaic level for the aberrant chromosome because of culture artifacts, and the abnormal cell line can decline after birth.
Assuntos
Nascido Vivo/genética , Mosaicismo/embriologia , Transtornos dos Cromossomos Sexuais/diagnóstico , Trissomia/diagnóstico , Adulto , Amniocentese , Cromossomos Humanos X/genética , Hibridização Genômica Comparativa , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Recém-Nascido , Cariótipo , Gravidez , Aberrações dos Cromossomos Sexuais/embriologia , Transtornos dos Cromossomos Sexuais/embriologia , Transtornos dos Cromossomos Sexuais/genética , Trissomia/genéticaRESUMO
OBJECTIVE: We present prenatal diagnosis of mosaicism for double aneuploidy of 47, XXY and trisomy 7 (48,XXY,+7) at amniocentesis in a pregnancy with a favorable outcome. CASE REPORT: A 33-year-old woman underwent amniocentesis at 17 weeks of gestation because of an increased risk for Down syndrome in maternal serum screening. Amniocentesis revealed a karyotype of 48,XXY,+7[8]/46,XY[16]. Simultaneous array comparative genomic hybridization (aCGH) analysis on uncultured amniocytes revealed the result of arr [GRCh37] (7) × 3 [0.54], (X) × 2 [0.52], (Y) × 1, compatible with trisomy 7 mosaicism and Klinefelter syndrome mosaicism. The parental karyotypes and prenatal ultrasound findings were normal. Repeat amniocentesis performed at 23 weeks of gestation revealed a karyotype of 48,XXY,+7[13]/46,XY[7]. Simultaneous molecular cytogenetic analyses on uncultured amniocytes revealed 30% mosaicism for 48,XXY,+7 by aCGH and 37% (37/100 cells) mosaicism for trisomy 7 and disomy X by interphase fluorescence in situ hybridization (FISH) analysis. Polymorphic DNA marker analysis excluded uniparental disomy (UPD) 7 and indicated a maternal origin of the chromosome aberration. The pregnancy was continued to 39 weeks of gestation, and a 3070-g healthy male baby was delivered. The cord blood had a karyotype of 46,XY, the umbilical cord had a karyotype of 48,XXY,+7[3]/46,XY[37], and the placenta had a karyotype of 48,XXY,+7. At age one month, the neonate was phenotypically normal, and interphase FISH analysis revealed 4.8% (5/105 cells) mosaicism on buccal mucosal cells and 8.9% (8/90 cells) mosaicism on urinary cells for trisomy 7 and disomy X, compared with 2% in normal control. Interphase FISH analysis on buccal mucosal cells at age two months revealed normal findings in 100/100 cells. CONCLUSION: Mosaic 48,XXY,+7 at amniocentesis without UPD 7 can be associated with a favorable fetal outcome. Cytogenetic discrepancy between cultured amniocytes and uncultured amniocytes may occur in mosaic 48,XXY,+7 at amniocentesis.
Assuntos
Amniocentese , Aneuploidia , Nascido Vivo/genética , Aberrações dos Cromossomos Sexuais/embriologia , Trissomia/genética , Dissomia Uniparental/genética , Adulto , Cromossomos Humanos Par 7/genética , Hibridização Genômica Comparativa , Análise Citogenética , Feminino , Humanos , Hibridização in Situ Fluorescente , Recém-Nascido , Cariótipo , Cariotipagem , Masculino , Mosaicismo/embriologia , GravidezRESUMO
OBJECTIVE: This study aimed to investigate the outcomes of patients who had preimplantation genetic testing for chromosomal structural rearrangement (PGT-SR) or for aneuploidy screening (PGT-A) with different indications. METHODS: This was a retrospective study at a single center. Pregnancy outcomes of all couples who had PGT from 2014 to 2018 were retrospectively analyzed, and the cumulative pregnancy rates (CPR) and the cumulative live birth/ongoing pregnancy rate (CLB/OPR) per patient with at least one transfer cycle were calculated. RESULTS: A total of 313 PGT-SR cycles of 255 patients, 22 PGT-sexing cycles of 20 patients, and 190 PGT-A cycles of 168 patients were performed during the period. In PGT-SR, the overall CPR and the CLB/OPR were 68.04% and 59.79%, respectively. In PGT-A, the CPR and CLB/OPR were 67.52% and 58.12%, respectively. We also found that the CPR (93.75%) and CLB/OPR (87.50%) were highest in patients for PGT-sexing with a diagnosis of Y chromosomal microdeletion. In addition, we discovered a significant trend that aneuploidy rate significantly increased with maternal age (p = 0.000) in PGT-A population. No significant difference was found in the mosaicism rate or clinical outcomes among the age groups. Similarly, the significance was absent in the PGT-SR population. CONCLUSION: We reviewed the CPR and CLB/OPR for different indications since the 24-chromosome technique has been applied in the clinical setting for 4 years in our center. We hope that our results will provide some pointed guidance and a new perspective on outcomes for PGT in certain patients and clinicians.
Assuntos
Transferência Embrionária/estatística & dados numéricos , Testes Genéticos/estatística & dados numéricos , Nascido Vivo , Taxa de Gravidez , Diagnóstico Pré-Implantação/estatística & dados numéricos , Adulto , Aneuploidia , Feminino , Testes Genéticos/métodos , Humanos , Gravidez , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Aberrações dos Cromossomos Sexuais/embriologia , Adulto JovemRESUMO
BACKGROUND: The present study aimed to determine the accuracy (Z-value) of non-invasive prenatal testing (NIPT) results for sex chromosome aneuploidy (SCA) in routine clinical practice. METHODS: Among a cohort of 12505 pregnant females, maternal plasma samples collected from our hospital were utilized for SCA analysis by NIPT detection. The positive samples were validated through an invasive procedure and karyotyping analysis. The predictive value from positive samples in sex chromosomes was compared to analyze the accuracy of the Z-value. RESULTS: There were 65 females with sex chromosome abnormalities within 12,505 pregnant females in the NIPT detection, which was validated by karyotype analysis of amniotic fluid puncture through sequencing, as well as bioinformatics analysis, with 18 true-positive samples. The true-positive results with 45,X, 47,XXY, 47,XXX and 47,XYY karyotypes predicted by NIPT were 14.29%, 50.00%, 66.67% and 71.43%, respectively. Among sex chromosome cases, the findings indicated that positive NIPT results with Z ≥ 9 show a higher accuracy. CONCLUSIONS: The findings of the present study demonstrate that the positive predictive value of NIPT for sex chromosome abnormalities is distinctive. The positive predictive value was highest for 47,XYY and lowest for 45,X. Additionally, the Z-value results are considered to be correlated with the accuracy of NIPT, although further studies need to be made.
Assuntos
Diagnóstico Pré-Natal/métodos , Aberrações dos Cromossomos Sexuais/embriologia , Transtornos dos Cromossomos Sexuais/diagnóstico , Transtornos dos Cromossomos Sexuais/genética , Cromossomos Humanos X/genética , Estudos de Coortes , Feminino , Testes Genéticos/métodos , Humanos , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Valor Preditivo dos Testes , Gravidez , Aberrações dos Cromossomos Sexuais/estatística & dados numéricos , Transtornos dos Cromossomos Sexuais/sangue , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Cromossomos Sexuais/patologia , Trissomia/diagnóstico , Trissomia/genética , Síndrome de Turner/diagnóstico , Síndrome de Turner/genética , Cariótipo XYY/diagnóstico , Cariótipo XYY/genéticaRESUMO
OBJECTIVE: To analyze the non-invasive prenatal testing (NIPT) for aneuploidy results of 31 515 singleton pregnancies in Fujian province, southeastern China, and assess its performance in low-, moderate- and high-risk pregnancies. METHODS: Women were categorized into groups according to whether their risk for fetal abnormality was low, moderate or high. Cell-free plasma DNA extracted from peripheral blood samples was subjected to low-coverage whole-genome sequencing. Standard Z-score analysis of the mapped sequencing reads was used to identify fetal aneuploidy, including the three main trisomies (T21, T18 and T13) and sex chromosome aneuploidy (SCA). NIPT-positive results were confirmed by amniocentesis and karyotyping. The performance of NIPT for detection of T21, T18, T13 and SCA was assessed by calculating the sensitivity and specificity. RESULTS: The rate of chromosomal abnormality detected by NIPT in the study population was 1.38%. A higher rate of chromosomal abnormality was found in the high-risk group (1.57%) compared to the moderate-risk (1.05%) and low-risk (1.18%) groups (P < 0.05). Sensitivity and specificity, respectively, were 98.96% (95/96) and 99.94% (31 274/31 292) for detection of T21, 100% (25/25) and 99.96% (31 352/31 363) for T18, 100% (7/7) and 99.97% (31 373/31 381) for T13 and 100% (61/61) and 99.74% (31 245/31 327) for SCA. Positive predictive values were high for T21 (84.07%) and T18 (69.44%) and moderate for T13 (46.67%) and SCA (42.66%). CONCLUSION: Our findings support the application of NIPT for reliable and accurate testing of the general population of reproductive-age women for clinically significant fetal aneuploidy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Aneuploidia , Ácidos Nucleicos Livres/análise , Aberrações Cromossômicas/embriologia , Transtornos Cromossômicos/diagnóstico , Teste Pré-Natal não Invasivo/métodos , Adulto , China , Transtornos Cromossômicos/embriologia , Feminino , Humanos , Gravidez , Gravidez de Alto Risco , Sensibilidade e Especificidade , Aberrações dos Cromossomos Sexuais/embriologia , Trissomia/diagnósticoRESUMO
Sex chromosome trisomies (SCT) are among the most common chromosomal duplications in humans. Due to recent technological advances in non-invasive screening, SCT can already be detected during pregnancy. This calls for more knowledge about the development of (young) children with SCT. This review focused on neurocognitive functioning of children with SCT between 0 and 18 years, on domains of global intellectual functioning, language, executive functioning, and social cognition, in order to identify targets that could benefit from early treatment. Online databases were used to identify peer-reviewed scientific articles using specific search terms. In total 18 studies were included. When applicable, effect sizes were calculated to indicate clinical significance. Results of the reviewed studies show that although traditionally, the focus has been on language and intelligence (IQ) in this population, recent studies suggest that executive functioning and social cognition may also be significantly affected already in childhood. These findings suggest that neuropsychological screening of children diagnosed with SCT should be extended, to also include executive functioning and social cognition. Knowledge about these neurocognitive risks is important to improve clinical care and help identify targets for early support and intervention programs to accommodate for the needs of individuals with SCT.
Assuntos
Transtornos Neurocognitivos/genética , Aberrações dos Cromossomos Sexuais/embriologia , Cromossomos Sexuais/genética , Adolescente , Criança , Pré-Escolar , Cognição , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes Neuropsicológicos , Gravidez , TrissomiaRESUMO
Maternal copy number variation (CNV), especially at the X chromosome is an important cause of false positive noninvasive prenatal test (NIPT) results for sex chromosomal aneuploidy. In addition, some maternal CNV can cause significant anomalies if the male fetus was inherited the X chromosome with CNV. During 1000 high risk Korean NIPT, we incidentally detected two cases of maternal X chromosomal CNV which can cause abnormal phenotype in a male fetus. The first false-positive NIPT case (47, XXY) was due to a maternal 0.5 Mb duplication at Xq28, including the MECP2 gene. The second is a case of an 8-Mb deletion on maternal Xq24q25, including GRIA3 and XIAP genes.
Assuntos
Cromossomos Humanos X/genética , Variações do Número de Cópias de DNA/genética , Testes Genéticos/métodos , Diagnóstico Pré-Natal/métodos , Aberrações dos Cromossomos Sexuais/embriologia , Adulto , Aneuploidia , Reações Falso-Positivas , Feminino , Humanos , Masculino , GravidezRESUMO
To evaluate the clinical performance of noninvasive prenatal screening (NIPS) for fetal sex chromosome aneuploidies (SCAs), pregnant women were recruited in this retrospective observational study. The NIPS test was undertaken using high-throughput gene sequencing. In total,50,301 pregnant women were analysed for demographic characteristics and medical history. Of them, 308 women (0.61%) had high risk for fetal SCAs, including 138 for 45,X, 111 for 47,XXY, 42 for 47,XXX, and 17 for 47,XYY. After the pre-test counselling, 182 participants chose to undergo invasive prenatal diagnosis, confirming 59 positive cases. The combined positive predictive value of NIPS was 32.42% (59/182), 18.39% (16/87), 44.4% (12/27), 39.29% (22/56), and 75% (9/12) for detecting SCAs, 45,X, 47,XXX, 47,XXY, and 47,XYY, respectively. NIPS can be a useful method to detect the fetal SCAs using high-throughput gene sequencing, though accuracy can still be improved, especially for 45,X. Although the value of NIPS compare favorably with those seen in traditional screening approaches for SCAs, it is important to highlight the limitations of NIPS while educating clinicians and patients.
Assuntos
Teste Pré-Natal não Invasivo/métodos , Diagnóstico Pré-Natal/métodos , Aberrações dos Cromossomos Sexuais/embriologia , Aneuploidia , China , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Cariotipagem/métodos , Gravidez , Estudos Retrospectivos , Aberrações dos Cromossomos Sexuais/classificação , Cromossomos Sexuais/genética , Trissomia/diagnóstico , Trissomia/genéticaRESUMO
A high incidence of aneuploidy is observed in vitro fertilization (IVF)-derived embryos, but the formation and repair mechanisms are unknown. Here, we investigated the effects of slightly increased reactive oxygen species (ROS) produced by in vitro culture conditions on embryo aneuploidy and the roles of the spindle assembly checkpoint (SAC) protein, mitotic arrest-deficient 2 (MAD2), and the DNA damage response (DDR) protein, checkpoint kinase 1 (CHK1), in aneuploidy repair. By assessing chromosome abnormalities via DAPI staining, karyotype analysis and next-generation sequencing technology, we demonstrated that mild oxidative damage mainly increased the risk of sex chromosome aneuploidy in male mouse embryos (41,XXY,+X and 41,XYY,+Y) through chromosome mis-segregation during the first mitosis. Isobaric tags for relative and absolute quantitation technology revealed that mild oxidative damage inhibited the expression of male reproduction-related proteins, including a kinase anchor protein 4 (AKAP4), whose gene is located on mouse/human Chromosome X. Under mild oxidative damage, abrogation of MAD2 by MAD2 inhibitor-1 (M2I-1) or CHK1 by siRNA microinjection increased sex chromosome mosaicism rate and reduced mitosis-promoting factor (MPF) activity. CHK1 inhibition also reduced kinetochore localization of centromere protein B (CENP B) and MAD2. These findings show that DDR and SAC are responsible for repair of sex chromosome mosaicism via the pCHK1 (S345)-CENP B/MAD2-MPF pathway; further, IVF may have negative effects on male offspring's reproduction ability, which ultimately depends on their continued repair capability. Therefore, we suggest that antioxidants, especially those targeting improved CHK1-MAD2 function, may be a promising therapeutic strategy to reduce aneuploidy formation of IVF-derived embryos and to maintain genome integrity of embryo and offspring.
Assuntos
Proteína B de Centrômero/metabolismo , Quinase 1 do Ponto de Checagem/metabolismo , Proteínas Mad2/metabolismo , Aberrações dos Cromossomos Sexuais/embriologia , Cromossomos Sexuais/genética , Aneuploidia , Animais , Células Cultivadas , Quinase 1 do Ponto de Checagem/genética , Reparo do DNA , Embrião de Mamíferos , Feminino , Fertilização in vitro , Humanos , Pontos de Checagem da Fase M do Ciclo Celular , Masculino , Mesotelina , Camundongos , Mitose , Estresse Oxidativo , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: To assess the application value in prenatal diagnosis using karyotype analysis combined with BACs-on-Beads (BoBs) assay. METHODS: Nine hundred sixty five pregnant women were subjected to amniocentesis, chromosomal karyotype analysis and detection of BoBs were employed simultaneously for abnormal number of chromosomes and 9 chromosome microdeletion syndrome in prenatal diagnosis. RESULTS: Fifty cases common chromosome aneupoidies were successfully detected by both karyotype analysis and BoBs which included 31 cases of trisomy 21,10 cases of trisomy 18 and 9 cases with sex chromosome abnormality. BoBs in addition detected 1 case of DiGeorge-1 microdeletion syndrome and 1 case of 7q11.23 microduplication syndrome. All 9 fetuses with chromosome abnormalities detected by karyotyping were missed by BoBs, including 2 cases of marker chromosomes,4 cases of chromosomal translocation,1 case of chromosomal inversion, 2 cases of Sex chromosome mosaicism; 2 cases of fetal inherited from the parents,7 cases for novel mutations. CONCLUSION: Karyotype analysis combined with BoBs dedtection is a rapid, effective and highly accurate prenatal diagnosis model that may should be widely used in clinical diagnosis.
Assuntos
Transtornos Cromossômicos/genética , Doenças Fetais/genética , Cariotipagem/métodos , Diagnóstico Pré-Natal/métodos , Adulto , Aberrações Cromossômicas , Transtornos Cromossômicos/embriologia , Cromossomos Artificiais Bacterianos/genética , Feminino , Doenças Fetais/diagnóstico , Humanos , Cariotipagem/instrumentação , Masculino , Gravidez , Diagnóstico Pré-Natal/instrumentação , Aberrações dos Cromossomos Sexuais/embriologiaRESUMO
Circulating DNA fragments in a pregnant woman's plasma derive from three sources: placenta, maternal bone marrow, and fetus. Prenatal sequencing to noninvasively screen for fetal chromosome abnormalities is performed on this mixed sample; results can therefore reflect the maternal as well as the fetoplacental DNA. Although it is recommended that pretest counseling include the possibility of detecting maternal genomic imbalance, this seldom occurs. Maternal abnormalities that can affect a prenatal screening test result include disorders that affect the size and metabolism of DNA, such as B12 deficiency, autoimmune disease, and intrahepatic cholestasis of pregnancy. Similarly, maternal tumors, both benign and malignant, can release DNA fragments that contain duplications or deletions. Bioinformatics algorithms can subsequently interpret the raw sequencing data incorrectly, resulting in false-positive test reports of fetal monosomies or test failures. Maternal sex-chromosome abnormalities, both constitutional and somatic, can generate results that are discordant with fetal ultrasound examination or karyotype. Maternal copy-number variants and mosaicism for autosomal aneuploidies can also skew interpretation. A maternal etiology should therefore be considered in the differential diagnosis of prenatal cell-free DNA test failures, false-positive and false-negative sequencing results. Further study is needed regarding the clinical utility of reporting maternal incidental findings.
Assuntos
Transtornos Cromossômicos/diagnóstico , Achados Incidentais , Diagnóstico Pré-Natal/métodos , Aneuploidia , Ácidos Nucleicos Livres/análise , Ácidos Nucleicos Livres/sangue , Transtornos Cromossômicos/sangue , DNA/sangue , Feminino , Desenvolvimento Fetal , Feto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Cariotipagem , Gravidez , Análise de Sequência de DNA/métodos , Aberrações dos Cromossomos Sexuais/embriologia , Ultrassonografia Pré-Natal/métodosRESUMO
BACKGROUND: Nance-Horan syndrome (NHS) is a rare X-linked developmental disorder characterized by congenital cataract, dental anomalies and facial dysmorphisms. Notably, up to 30% of NHS patients have intellectual disability and a few patients have been reported to have congenital cardiac defects. Nance-Horan syndrome is caused by mutations in the NHS gene that is highly expressed in the midbrain, retina, lens, tooth, and is conserved across vertebrate species. Although most pathogenic mutations are nonsense mutations, a few genomic rearrangements involving NHS locus have been reported, suggesting a possible pathogenic role of the flanking genes. METHODS: Here, we report a microdeletion of 170,6 Kb at Xp22.13 (17.733.948-17.904.576) (GRCh37/hg19), detected by array-based comparative genomic hybridization in an Italian boy with NHS syndrome. RESULTS: The microdeletion harbors the NHS, SCLML1, and RAI2 genes and results in a phenotype consistent with NSH syndrome and developmental delay. CONCLUSION: We compare our case with the previous Xp22.13 microdeletions and discuss the possible pathogenetic role of the flanking genes. Birth Defects Research 109:866-868, 2017. © 2017 Wiley Periodicals, Inc.
Assuntos
Catarata/congênito , Doenças Genéticas Ligadas ao Cromossomo X/genética , Anormalidades Dentárias/genética , Catarata/genética , Catarata/metabolismo , Deleção Cromossômica , Cromossomos Humanos X/genética , Códon sem Sentido , Hibridização Genômica Comparativa/métodos , Éxons/genética , Genes Ligados ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/metabolismo , Humanos , Lactente , Deficiência Intelectual/genética , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Proteínas de Membrana , Mutação , Proteínas Nucleares/genética , Linhagem , Fenótipo , Proteínas do Grupo Polycomb/genética , Proteínas/genética , Aberrações dos Cromossomos Sexuais/embriologia , Síndrome , Anormalidades Dentárias/metabolismoRESUMO
OBJECTIVE: To compare autosomal and sex chromosome aneuploidy rates of embryos derived from sperm with abnormal and normal parameters. DESIGN: Retrospective cohort study. SETTING: Assisted reproduction center. PATIENT(S): Three thousand eight hundred thirty-five embryos generated from 629 couples undergoing IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Incidence of aneuploidy in the trophectoderm of blastocyst embryos derived from standard IVF embryos and intracytoplasmic (ICSI) males with normal and oligozoospermic semen samples, in couples with donor eggs (mean maternal age, 25.0 years) and their own eggs (mean maternal age, 35.4 years). RESULT(S): The rate of sex chromosome aneuploidy was significantly (around threefold) higher in the oligozoospermic group compared with in both control groups (standard vs. ICSI insemination). This applied whether donor (young) or own (older) eggs were used. Significant differences were seen in the oligozoospermic samples for autosomes 1, 2, 11 (own eggs), and 18 (donor eggs) compared with both control groups; however, no significant difference was seen between each of the treatment groups for the overall rate of autosomal aneuploidy. No significant differences were seen between the two control groups (normozoospermic males, standard vs. ICSI insemination) in either of the egg group types for any chromosome pairs. CONCLUSION(S): Severe male factor infertility is associated with a significant increase in the occurrence of sex chromosome abnormalities in blastocyst embryos compared with in embryos derived from normal semen samples. Aneuploidy rates in embryos derived from sperm with normal parameters were not significantly different whether ICSI or standard insemination was used to achieve fertilization. These results highlight severe male factor infertility as a possible referral category for preimplantation comprehensive chromosomal screening.
Assuntos
Aneuploidia , Blastocisto , Análise do Sêmen/efeitos adversos , Aberrações dos Cromossomos Sexuais , Adulto , Blastocisto/metabolismo , Blastocisto/patologia , Feminino , Fertilização in vitro , Humanos , Infertilidade Masculina/genética , Masculino , Gravidez , Diagnóstico Pré-Implantação , Estudos Retrospectivos , Fatores de Risco , Aberrações dos Cromossomos Sexuais/embriologia , Aberrações dos Cromossomos Sexuais/estatística & dados numéricos , Espermatozoides/patologiaRESUMO
PURPOSE: To examine combined first trimester screening (FTS), noninvasive prenatal testing (NIPT) and a two-step policy that combines FTS and NIPT in screening for aneuploidy. MATERIALS AND METHODS: Retrospective study involving 21,052 pregnancies where FTS was performed at the Praxis Praenatal.de in Duesseldorf, Germany. In each case, the sum risk of trisomy 21, 18 and 13 was computed. We assumed that NIPT detects 99 %, 98 %, 90 % and 99 % of cases with trisomy 21, 18, 13 and sex chromosomal abnormalities and that the false-positive rate is 0.5 %. The following screening policies were examined: NIPT or FTS with sum risk cut-offs of 1 in 50 and 1 in 250 in all patients or a two-step-policy with FTS in all patients followed by NIPT in the intermediate sum risk group. For the intermediate risk group, sum risk cut-offs of 1 in 50 and 1 in 1000 and 1 in 150 and 1 in 500 were used. RESULTS: There were 127, 34, 13 and 15 pregnancies with trisomy 21, 18, 13 and sex chromosomal abnormalities. 23 fetuses had other chromosomal abnormalities with an increased risk for adverse outcome that are not detectable by NIPT. 20,840 pregnancies were classified as normal as ante- and postnatal examinations did not show any signs of clinically significant chromosomal abnormalities. FTS with a sum risk cut-off of 1 in 50 and 1 in 250 detects 81 % and 91 % for all aneuploidies. NIPT detects 88 % of the respective pregnancies. The 2-step approach with sum risk cut-offs of 1 in 50 and 1 in 1000 detects 94 % of all aneuploidies. With sum risk cut-offs of 1 in 150 and 1 in 500, the detection rate is 93 %. CONCLUSION: A 2-step policy with FTS for all patients and NIPT in the intermediate risk group results in the highest detection rate of all aneuploidies.
Assuntos
Aberrações Cromossômicas , Primeiro Trimestre da Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Adulto , Transtornos Cromossômicos/diagnóstico por imagem , Transtornos Cromossômicos/embriologia , Cromossomos Humanos Par 13/diagnóstico por imagem , Cromossomos Humanos Par 18/diagnóstico por imagem , Síndrome de Down/diagnóstico por imagem , Síndrome de Down/embriologia , Feminino , Alemanha , Humanos , Valor Preditivo dos Testes , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Aberrações dos Cromossomos Sexuais/embriologia , Trissomia , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18RESUMO
OBJECTIVE: To study whether pregnant women would like to be informed if sex chromosomal abnormalities (SCA) were suspected with the non-invasive prenatal diagnosis of fetal Down syndrome (the NIFTY) test. METHODS: Two hundred and one patients carried a singleton pregnancy requesting the NIFTY test were invited to give their preferences if there was suspicion of SCA by the NIFTY test. RESULTS: Over 93.5% were ethnic Chinese, with a mean age of 36. Prior Down screening was positive in 66 (32.8%). Over 50% of subjects considered SCA to be better in terms of disability compared to Down syndrome, and only 5.2% considered SCA to be worse. Yet, the majority (198, 98.5%) indicated that they wanted to be informed if there was suspicion of SCA. Of whom 34.8% would have an amniocentesis for confirmation, while 57.1% were not certain, indicating the possibility of accepting these conditions. CONCLUSION: Besides screening Down syndrome by NIFTY, most pregnant women would also like to be informed if there was suspicion of SCA. Those screened positive should be counseled by those with experience in genetics to avoid unnecessary pregnancy termination.
Assuntos
Doenças Fetais/diagnóstico , Doenças Fetais/genética , Gestantes/psicologia , Diagnóstico Pré-Natal/psicologia , Aberrações dos Cromossomos Sexuais , Adulto , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Testes Genéticos , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Percepção/fisiologia , Gravidez , Aberrações dos Cromossomos Sexuais/embriologia , Inquéritos e Questionários , Adulto JovemRESUMO
Identification of the 47,XXX karyotype often occurs adventitiously during prenatal fetal karyotyping in cases of advanced maternal age. Although most females with 47,XXX appear healthy at birth, various types of congenital malformations have been reported, of which urinary tract anomalies are the most frequent. We report on 2 newborns with 47,XXX and congenital cardiac defects, one of whom had duodenal atresia and the other an occipital encephalocele. This expands the spectrum of malformations reported in association with the triple-X syndrome. We also present a review of the literature on non-urinary tract malformations in females with 47,XXX. We conclude that prenatal identification of the 47,XXX karyotype is an indication for detailed fetal ultrasonography which should include examination of multiple organ systems. Such prenatal screening for possible associated congenital malformations should help to ensure optimal perinatal clinical management of 47,XXX cases.
Assuntos
Cromossomos Humanos X/genética , Encefalocele/genética , Cardiopatias Congênitas/genética , Atresia Intestinal/genética , Aberrações dos Cromossomos Sexuais/embriologia , Adulto , Amniocentese , Aneuploidia , Encefalocele/diagnóstico , Encefalocele/cirurgia , Feminino , Idade Gestacional , Cardiopatias Congênitas/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/cirurgia , Atresia Intestinal/diagnóstico , Atresia Intestinal/cirurgia , Cariotipagem , Gravidez , Ultrassonografia Pré-NatalRESUMO
OBJECTIVES: To examine abnormal fertilization phenomena in blastomeres of embryos generated from conventional IVF and ICSI displaying a single pronucleus at the zygote stage. METHODS: 132 embryos from monopronuclear zygotes (1PN) generated from conventional IVF and ICSI were examined by FISH (fluorescent in situ hybridization) with X, Y dual color centromere probes. RESULTS: In the embryos that were obtained from conventional IVF, the percentage of diploid, monoploid and mosaic sex chromosome were 54.35, 23.91 and 21.74%, respectively. In the embryos from 1PN zygotes derived from ICSI, the percentage of diploid, monoploid and mosaic sex chromosomes were 31.51, 31.51 and 36.99%, respectively. For monoploid embryos, the ratio of XO was significantly higher than that of YO in both conventional IVF and ICSI groups. CONCLUSION: The results demonstrated that the majority of embryos derived from 1PN zygotes generated with conventional IVF or ICSI have a high incidence of aneuploidy. Furthermore, the sex chromosome diploid ratio of embryos from 1PN zygotes derived from conventional IVF was significantly higher than those generated from ICSI procedure in Chinese women. Nevertheless, the high proportion of aneuploid embryos suggests that such embryos should not be utilized for embryo transfer.
Assuntos
Cromossomos Humanos X , Fertilização in vitro/efeitos adversos , Aberrações dos Cromossomos Sexuais/embriologia , Injeções de Esperma Intracitoplásmicas/efeitos adversos , Zigoto/ultraestrutura , Adulto , Aneuploidia , Feminino , Humanos , Hibridização in Situ Fluorescente , GravidezAssuntos
Quimera/genética , Cromossomos Humanos Par 9 , Cromossomos Humanos X , Cromossomos Humanos Y , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Policitemia Vera/genética , Aberrações dos Cromossomos Sexuais , Trissomia/genética , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Medula Óssea/patologia , Quimera/embriologia , Progressão da Doença , Fertilidade , Humanos , Hidroxiureia/uso terapêutico , Mesilato de Imatinib , Hibridização in Situ Fluorescente , Achados Incidentais , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Células-Tronco Neoplásicas/ultraestrutura , Piperazinas/uso terapêutico , Policitemia Vera/complicações , Policitemia Vera/tratamento farmacológico , Policitemia Vera/patologia , Pirimidinas/uso terapêutico , Aberrações dos Cromossomos Sexuais/embriologiaRESUMO
Studies on tooth crown size and structure in families and in individuals with various sex chromosome anomalies have demonstrated differential direct effects of the human X and Y chromosome genes on growth. The Y chromosome promotes both tooth crown enamel and dentin growth, whereas the effect of the X chromosome on crown growth seems to be restricted to enamel formation. Enamel growth is decisively influenced by cell secretory function and dentin growth by cell proliferation. It is suggested that these differential effects of the X and Y chromosomes on growth explain the expression of sexual dimorphism in various somatic features. These include tooth crown and root size, crown shape and the number of the teeth, and under the assumption of genetic pleiotropy, torus mandibularis, statural growth, and sex ratio. It is of interest that molecular studies have shown that the gene loci for human amelogenin, the major protein component of the organic matrix in enamel are on both the X and Y chromosomes. Future questions include the role of the Y chromosome in the mineralization process, the concentric control of enamel and dentin growth, and gene expression.