Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
BMC Pregnancy Childbirth ; 23(1): 568, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37543573

RESUMO

BACKGROUND: Previous observational cohort studies have shown that the composition of the gut microbiota is related to the risk of intrahepatic cholestasis of pregnancy (ICP), although it is unclear if the association is causative. This study used Mendelian randomization (MR) to systematically examine whether the gut microbiota was causally linked to ICP. METHODS: We obtained the genome-wide association study (GWAS) summary statistics of gut microbiota and ICP from published GWASs. Maximum likelihood (ML), MR-Egger regression, weighted median, inverse variance weighted (IVW), and weighted model were used to investigate the causal association between gut microbiota and ICP. We further conducted a series of sensitivity analyses to confirm the robustness of the primary results of the MR analyses. Reverse MR analysis was performed on the bacterial taxa that were reported to be causally linked to ICP risk in forwarding MR analysis to evaluate the possibility of reverse causation. RESULTS: MR analysis revealed that phylum Tenericutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), class Bacteroidia (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), class Mollicutes (OR: 1.670, 95%CI: 1.073-2.598, P = 0.023), and order Bacteroidales (OR: 1.644, 95%CI: 1.031-2.622, P = 0.037), and were positively associated with the risk of ICP. And we identified that the relative abundance of genus Dialister (OR: 0.562, 95%CI: 0.323-0.977, P = 0.041), genus Erysipelatoclostridium (OR: 0.695, 95%CI: 0.490-0.987, P = 0.042), genus Eubacterium (brachy group) (OR: 0.661, 95%CI: 0.497-0.880, P = 0.005), genus Eubacterium (hallii group) (OR: 0.664, 95%CI: 0.451-0.977, P = 0.037), genus Holdemania (OR: 0.590, 95%CI: 0.414-0.840, P = 0.003), genus Ruminococcus (torques group) (OR: 0.448, 95%CI: 0.235-0.854, P = 0.015), and genus Veillonella (OR: 0.513, 95%CI: 0.294-0.893, P = 0.018) were related to a lower risk of ICP. Additional sensitivity analyses confirmed the robustness of the association between specific gut microbiota composition and ICP. No evidence of reverse causality from ICP to identified bacterial taxa was found in the findings of the reverse MR analyses. CONCLUSIONS: Under MR assumptions, our findings propose new evidence of the relationship between gut microbiota and ICP risk. Our results show that the gut microbiota may be useful target of intervention for ICP.


Assuntos
Microbioma Gastrointestinal , Feminino , Gravidez , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Bacteroidetes
2.
Food Funct ; 14(16): 7682-7691, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37540124

RESUMO

The trimester-specific associations of maternal dietary patterns with preterm birth (PTB) are unclear. In a prospective prebirth cohort study, we aimed to examine the critical time window of maternal prenatal dietary patterns and the risk of PTB. We assessed prenatal dietary intake among 1500 pregnant women with validated food frequency questionnaires during the 1st, 2nd and 3rd trimester, respectively. We used logistic regression models and generalized estimating equation models to examine the trimester-specific associations and longitudinal associations between maternal dietary patterns in relation to risk of PTB and PTB subtypes. The incidence rate of PTB was 11.9% (179 out of 1500 pregnant women) in the present study. We observed that maternal adherence to a fish-seafood pattern in the 1st trimester was associated with higher risk of PTB [tertile 3 (T3) vs. tertile 1 (T1): OR = 2.29, 95% CI: 1.32-3.96] and iatrogenic preterm birth (IPTB) (T3 vs. T1: OR = 2.26, 95% CI: 1.21-4.20), while a fish-seafood pattern in the 2nd trimester was associated with lower risk of PTB (T3 vs. T1: OR = 0.49, 95% CI: 0.25-0.93). Maternal adherence to a dairy-egg pattern in the 2nd or 3rd trimester was associated with higher risks of PTB and IPTB. No dietary patterns were associated with spontaneous preterm birth. Our findings provide new evidence that specific dietary patterns during different trimesters may have different and even inverse health effects on pregnant women. This supports the necessity of guiding the maternal diet according to different periods of pregnancy to prevent PTB.


Assuntos
Nascimento Prematuro , Recém-Nascido , Animais , Gravidez , Feminino , Humanos , Nascimento Prematuro/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Universidades , Dieta , China/epidemiologia
4.
Reprod Sci ; 30(1): 93-110, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35352330

RESUMO

This study was to assess the effectiveness of cervical pessary combined with vaginal progesterone for the prevention of preterm birth (PTB). Ten studies about singleton [five randomized controlled trials (RCTs), vs vaginal progesterone; four cohorts, vs vaginal progesterone; two cohorts, vs cervical cerclage + vaginal progesterone] and two cohort studies about multiple pregnancies (vs vaginal progesterone) were included after searching electronic databases. For singleton pregnancies, the meta-analysis of three non-RCTs [relative risk (RR) = 0.41, p = 0.001] or total trials in non-Asian country (RR = 0.56, p = 0.03) revealed that compared with vaginal progesterone alone, cervical pessary + vaginal progesterone treatment had significant effectiveness on preventing PTB < 34 weeks, but not for five RCTs; meta-analysis of two trials showed that cervical pessary + vaginal progesterone had no significant prevention effects of PTB compared with cervical cerclage + vaginal progesterone. For multiple pregnancies, meta-analysis of two trials showed that compared with vaginal progesterone, cervical pessary + vaginal progesterone treatment increased neonatal birth weight (standardized mean difference = 0.50, p = 0.01). Trial sequential analysis implied additional studies were required. Four studies vs other controls (pessary, three-combined, tocolysis, conservative or no treatment; one study, each) were selected for systematic review. In conclusion, cervical pessary combined with vaginal progesterone may be safe and effective to prevent PTB in singleton pregnancies and increase neonatal birth weight in the multiple pregnancies compared with vaginal progesterone alone.


Assuntos
Nascimento Prematuro , Progesterona , Gravidez , Recém-Nascido , Feminino , Humanos , Progesterona/uso terapêutico , Nascimento Prematuro/prevenção & controle , Pessários , Peso ao Nascer , Colo do Útero , Administração Intravaginal
5.
Comput Biol Med ; 147: 105801, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35785663

RESUMO

Fetal head circumference (HC) is an important biological index in prenatal ultrasound screening. In the clinic, fetal HC is usually measured manually by sonographers in two dimensional (2D) ultrasound images. The manual method is significantly affected by the inter/intra-observer difference and the process of manual measurement is inconvenient and time-consuming for sonographers. Although several artificial intelligence (AI) approaches had been applied to fetal HC measurement, they had weak generalization ability, especially for the incomplete or blurred skull edge. In this study, a fast and accurate method for fetal HC auto-measurement was proposed. Different from the common region segmentation method, an end-to-end convolutional neural network (CNN) for fetal skull boundary segmentation in 2D ultrasound images is proposed, which is an efficient method to directly segment the boundary of fetal skull by using the proposed double-branch structure. The segmentation results can be directly used to calculate fetal HC without complex post-processing. The proposed approach achieved excellent results: Mean Dice Sore (MDS)±std: 97.98 ± 1.30, Mean Hausdorff Distance (MHD)±std: 1.20 ± 0.68 mm, Mean Absolute Difference (MAD)±std: 1.75 ± 1.60 mm, Mean Difference (MD)±std: 0.08 ± 2.37 mm. Additionally, we drew a Bland-Altman plot to demonstrate that HC measured by the proposed approach has high agreement with the real value. Comprehensive results show that the proposed approach is comparable to the state-of-the-art methods for fetal HC measurement. Meanwhile, our approach belongs to a lightweight network with less parameters, which is convenient for deployment. We hope it could provide help for precision medicine in prenatal ultrasound screening.


Assuntos
Inteligência Artificial , Infecções Sexualmente Transmissíveis , Feminino , Cabeça/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Gravidez , Ultrassonografia/métodos
6.
Front Med (Lausanne) ; 9: 848904, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35425784

RESUMO

Fetal head circumference (HC) is an important biological parameter to monitor the healthy development of the fetus. Since there are some HC measurement errors that affected by the skill and experience of the sonographers, a rapid, accurate and automatic measurement for fetal HC in prenatal ultrasound is of great significance. We proposed a new one-stage network for rotating elliptic object detection based on anchor-free method, which is also an end-to-end network for fetal HC auto-measurement that no need for any post-processing. The network structure used simple transformer structure combined with convolutional neural network (CNN) for a lightweight design, meanwhile, made full use of powerful global feature extraction ability of transformer and local feature extraction ability of CNN to extract continuous and complete skull edge information. The two complement each other for promoting detection precision of fetal HC without significantly increasing the amount of computation. In order to reduce the large variation of intersection over union (IOU) in rotating elliptic object detection caused by slight angle deviation, we used soft stage-wise regression (SSR) strategy for angle regression and added KLD that is approximate to IOU loss into total loss function. The proposed method achieved good results on the HC18 dataset to prove its effectiveness. This study is expected to help less experienced sonographers, provide help for precision medicine, and relieve the shortage of sonographers for prenatal ultrasound in worldwide.

7.
Cancer Biother Radiopharm ; 37(7): 569-579, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33794097

RESUMO

Background: As one of the three malignant genital tumors, mortality in women with ovarian cancer is consistently high worldwide. It is of great importance to find prognostic markers for diagnosis and treatment of ovarian cancer. In this study, the authors utilized the bioinformatics analysis to identify the potential key genes to reveal the potential mechanism for ovarian cancer. Materials and Methods: The authors used the gene expression profile (GSE14407) to perform differentially expressed gene (DEG) analysis and the weighted gene co-expression network analysis. They selected the key module and performed the gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the genes in the hub module. Then they screened the key genes in the hub module, and further validated their expression level. Results: A total of 3124 DEGs were detected after differential gene expression analysis; of these, 433 were upregulated genes and 2691 were downregulated genes. The authors selected the brown module that is significantly associated with the BRCA gene expression. Then they selected 30 hub genes from the protein-protein interaction network. The authors identified the PDZ binding kinase (PBK) as the prognosis-associated hub gene whose expression was significantly high in the ovarian cancer tissue. Conclusions: The bioinformatics analysis for the DEGs could be important to understand the pathogenesis for ovarian cancer. In this study, PBK is identified as a potential marker that might improve the understanding of the molecular mechanism and the diagnosis level for ovarian cancer.


Assuntos
Neoplasias Ovarianas , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Epitelial do Ovário/genética , Biologia Computacional , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Prognóstico
8.
Neural Regen Res ; 17(6): 1293-1298, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34782574

RESUMO

Studies in animals indicate that sevoflurane exposure in the second trimester of pregnancy has harmful effects on the learning and memory of offspring. Whether an enriched environment can reverse the damage of sevoflurane exposure in the second trimester of pregnancy on the learning and memory of rat offspring remains unclear. In this study, rats at 14 days of pregnancy were exposed to 3.5% sevoflurane for 2 hours and their offspring were treated with an enriched environment for 20 successive days. We found that the enriched environment for offspring increased nestin and Ki67 levels in hippocampal tissue, increased hippocampal neurogenesis, inhibited glycogen synthase kinase 3ß activity, and increased the expression of cell proliferation-related ß-catenin and apoptosis-related Bcl-2, indicating that an enriched environment reduces sevoflurane-induced damage by increasing the proliferation of stem cells in the hippocampus. These findings suggest that an enriched environment can reverse the effects of sevoflurane inhaled by rats during the second trimester of pregnancy on learning and memory of offspring. This study was approved by the Animal Ethics Committee of Shengjing Hospital of China Medical University (approval No. 2018PS07K) on January 2, 2018.

9.
BMC Pregnancy Childbirth ; 21(1): 595, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479507

RESUMO

BACKGROUND: Qualitative research can reflect the actual thoughts and experience of research subjects and can be used to explore the experiences of women presenting with twin-to-twin transfusion syndrome (TTTS) to facilitate the provision of targeted psychological support. METHODS: A semi-structured interview method was used to assess the pregnancy and parenting experiences of women with TTTS. Colaizzi method was used for data analysis. RESULTS: Eighteen women participated in the study. We found that women with TTTS during pregnancy experienced persistent worry about their children's health from the disease diagnosis to the subsequent parenting processes, even in case of minor changes in their children's health. The lack of an efficient referral process and health information increased their uncertainty about their children's health. CONCLUSION: In addition to the children's health, other difficulties encountered during pregnancy and parenting may aggravate the pressure. Clinicians in the first-visit hospital and foetal medicine centre should improve the referral process and establish a follow-up system to provide women with health information and psychological support.


Assuntos
Atitude Frente a Saúde , Transfusão Feto-Fetal/psicologia , Complicações na Gravidez/psicologia , Complicações na Gravidez/cirurgia , Gravidez de Gêmeos/psicologia , Gestantes/psicologia , Adulto , China , Feminino , Humanos , Entrevistas como Assunto , Gravidez , Pesquisa Qualitativa , Adulto Jovem
10.
Neurochem Res ; 46(8): 2046-2055, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34003417

RESUMO

Mild intrauterine hypoperfusion (MIUH) can induce placental dysfunction and lead to long-term changes during the process of brain development. A better understanding of the mechanism of MIUH will help in the development of new neuroprotective strategies for the placental chamber. To better understand the mechanism of the effect of MIUH on the neural development of offspring, we constructed a model of MIUH in pregnant rats. The proliferation, apoptosis, and autophagy of hippocampal neurons in fetal rats were studied via flow cytometry, immunofluorescence staining, JC-1 staining, western blotting, and real-time polymerase chain reaction at different time points (6, 24, 48, and 72 h). The results showed that MIUH significantly inhibited the proliferation of hippocampal neurons and promoted their apoptosis and autophagy. Simultaneously, MIUH could promote PTEN expression and affect the PTEN signaling pathway. bpV, an inhibitor of PTEN, could restore the inhibition of hippocampal nerve cell growth caused by MIUH. MIUH may inhibit neuronal proliferation and promote neuronal apoptosis and autophagy by regulating the PTEN signaling pathway.


Assuntos
Proliferação de Células/fisiologia , Hipóxia Fetal/fisiopatologia , Transtornos do Neurodesenvolvimento/fisiopatologia , Neurônios/metabolismo , Circulação Placentária/fisiologia , Transdução de Sinais/fisiologia , Animais , Apoptose/fisiologia , Autofagia/fisiologia , Constrição Patológica , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Feto , Pontos de Checagem da Fase G1 do Ciclo Celular/fisiologia , Hipocampo/patologia , Neurônios/patologia , Ovário/irrigação sanguínea , Ovário/patologia , PTEN Fosfo-Hidrolase/metabolismo , Gravidez , Ratos Sprague-Dawley , Artéria Uterina/patologia
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 847-850, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761592

RESUMO

OBJECTIVE: To diagnose a fetus with Papillorenal syndrome by prenatal ultrasonography and genetic testing, and to correlate its genotype with phenotype. METHODS: Ultrasound finding of the fetus was reviewed. Muscle sample of the abortus was taken, and genetic variant related to the clinical phenotype was screened by whole exome sequencing (WES). Suspected pathogenic variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound revealed severe dysplasia of the fetal kidneys and oligohydramnios. WES revealed that the fetus has carried a c.736G>T (p.Glu246Ter) nonsense variant of the PAX2 gene, which was unreported previously. The result of Sanger sequencing was consistent with that of WES. Both parents of the fetus were of the wild-type, suggesting a de novo origin of the fetal variant. CONCLUSION: The novel heterozygous c.736G>T (p.Glu246Ter) variant of the PAX2 gene probably underlay the Papillorenal syndrome in the fetus. Above finding has provided a basis for genetic counseling and clinical decision-making.


Assuntos
Coloboma/diagnóstico , Coloboma/genética , Feto , Testes Genéticos , Diagnóstico Pré-Natal , Insuficiência Renal/diagnóstico , Insuficiência Renal/genética , Refluxo Vesicoureteral/diagnóstico , Refluxo Vesicoureteral/genética , Feminino , Humanos , Fator de Transcrição PAX2/genética , Fenótipo , Gravidez , Sequenciamento do Exoma
12.
J Hum Genet ; 65(12): 1129-1134, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32655146

RESUMO

Congenital disorders of glycosylation (CDG) are a group of genetic, mostly multisystem disorders, which often involve the central nervous system. ALG3-CDG is one the some 130 known CDG. Here we report two siblings with a severe phenotype and intrauterine death. Whole-exome sequencing revealed two novel variants in ALG3: NM_005787.6:c.512G>T (p.Arg171Leu) inherited from the mother and NM_005787.6:c.511C>T (p.Arg171Trp) inherited from the father.


Assuntos
Sistema Nervoso Central/metabolismo , Defeitos Congênitos da Glicosilação/genética , Genes Letais/genética , Manosiltransferases/genética , Feto Abortado/patologia , Sistema Nervoso Central/patologia , Defeitos Congênitos da Glicosilação/metabolismo , Defeitos Congênitos da Glicosilação/patologia , Feminino , Humanos , Masculino , Mães , Mutação/genética , Fenótipo , Irmãos , Sequenciamento do Exoma
13.
Neural Regen Res ; 15(11): 2082-2088, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32394966

RESUMO

Mild intrauterine hypoperfusion (MIUH) is a serious pathological event that affects the growth and development of fetuses and offspring. MIUH can lead to growth restriction, low birth weight, neurodevelopmental disorders, and other adverse clinical outcomes. To study the effects of MIUH on learning and memory function in offspring, a model of MIUH was established by placing a coil (length 2.5 mm, diameter 0.24 mm) on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy (day 17). Next, 120 mg/kg lithium chloride (the MIUH + Li group) or normal saline (the MIUH group) was injected intraperitoneally into these rats. In addition, 120 mg/kg lithium chloride (the Li group) or normal saline (the SHAM group) was injected intraperitoneally into pregnant rats without coil placement. The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth. In the MIUH group, the escape latency and journey length before reaching the platform were both increased, and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group. Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67 (both cell-proliferation-related proteins) expression was significantly downregulated in the MIUH group compared with the SHAM group. Furthermore, western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats, and revealed that glycogen synthase kinase 3ß (GSK3ß) expression was upregulated and ß-catenin expression was downregulated in the MIUH group compared with the SHAM group. In addition, compared with the MIUH group, the expression levels of p-GSK3ß and ß-catenin were upregulated in the MIUH + Li group. These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3ß signaling pathway. The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University (approval No. 2018PS07K) in June 2018.

14.
Placenta ; 95: 84-90, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32452406

RESUMO

INTRODUCTION: Three-dimensional (3D) sonography combined with tomographic ultrasound imaging (TUI) to observe placental vascular anastomoses in monochorionic diamniotic (MCDA) twin pregnancies was evaluated. METHODS: Women with MCDA twin pregnancies at a gestational age of 16-32 weeks were enrolled in this retrospective study. Placental anastomoses were detected using two-dimensional (2D) and 3D sonography. Two-dimensional data were obtained by color and spectral Doppler and 3D data with high-definition flow within the area between twins' umbilical cord insertions. Volume post-processing using TUI mode identified anastomoses. Anastomotic findings on ultrasound were compared with fetoscopic surgery or postnatally injected placentas for diagnostic value. Anastomoses detection was compared between the two imaging modalities. RESULTS: Seventy-six twin pregnancies were analyzed: 11 selective intrauterine growth restrictions (sIUGR), 10 twin-to-twin transfusion syndrome (TTTS), and 55 without complications. Seventy-one twin pregnancies had arterio-arterial (AA) anastomoses and 75 had arterio-venous (AV) anastomoses. Three-dimensional sonography combined with TUI was more sensitive (87.3%) and accurate (88.2%) in detecting AA anastomoses than 2D sonography (74.6%, 76.3%, respectively; P < 0.05), but had comparable sensitivity for AV anastomoses. The specificity of both modalities for anastomoses was 100%. The detection rate of AA anastomoses by 3D modality was (40%) TTTS vs. (87.3%) normal (P < 0.05), but comparable (90.9%) for sIUGR. The detection rates of AV anastomoses (90%, 81.8%) in TTTS and sIUGR were comparable with (87.3%) normal (P > 0.05). DISCUSSION: Three-dimensional sonography combined with TUI highlighted placental anastomoses and may be useful for the clinical diagnosis and therapy of MCDA twin complications.


Assuntos
Anastomose Arteriovenosa/diagnóstico por imagem , Retardo do Crescimento Fetal/diagnóstico por imagem , Transfusão Feto-Fetal/diagnóstico por imagem , Placenta/diagnóstico por imagem , Ultrassonografia Pré-Natal/métodos , Adulto , Feminino , Humanos , Placenta/irrigação sanguínea , Gravidez , Estudos Retrospectivos
15.
Front Genet ; 10: 1161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31803239

RESUMO

Silver-Russell syndrome (SRS) is a rare, well-recognized disorder characterized by growth restriction, including intrauterine and postnatal growth. Most SRS cases are caused by hypomethylation of the paternal imprinting center 1 (IC1) in chromosome 11p15.5 and maternal uniparental disomy in chromosome 7 (UPD7). Here, we report on a Chinese family with a 4 year old male proband presenting with low birth weight, growth retardation, short stature, a narrow chin, delayed bone age, and speech delays, as a result of a rare molecular etiology. Whole-exome sequencing was conducted, and a novel de novo IGF2 splicing variant, NM_000612.4: c.157+5G > A, was identified on the paternal allele. In vitro functional analysis by RT-PCR and Sanger sequencing revealed that the variant leads to an aberrant RNA transcript lacking exon 2. Our results further confirm the IGF2 variant mediates SRS and expand the pathogenic variant and phenotypic spectrum of IGF2-mediated SRS. The results indicate that, beyond DNA methylation and UPD7 and CDKN1C variant tests, IGF2 gene screening should also be considered for SRS molecular diagnoses.

16.
Exp Ther Med ; 18(4): 2695-2700, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31572517

RESUMO

In the current study, one case of COG5-CDG involving a Chinese male patient with severe neurological symptoms, who had previously been misdiagnosed with congenital gyrus malformation, is described. A clinical investigation was performed and targeted next-generation sequencing (NGS) was used to identify COG5 variants in the patient and his family. PCR and Sanger sequencing were performed for the verification of NGS results. The patient showed severe central and peripheral neurological symptoms, while only mild symptoms were reported in a previous reported case, in which different mutations were involved. The reported patient carried the frameshift mutation c.330delT (p.V111Lfs*22), and a missense mutation c.2324 C>T (p.P775L) in the COG5 gene. The c.330delT (p.V111Lfs*22) variant is a novel mutation, while c.2324 C>T (p.P775L) has previously been reported. Inheriting one variant from each of his parents, the current case report furthers the understanding of genotype-phenotype correlations in COG5-CDG.

17.
Mol Genet Genomic Med ; 7(11): e967, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31478598

RESUMO

BACKGROUND: X-linked deafness-4 (DFNX4) caused by functional loss of SMPX is a nonsyndromic form of progressive hearing loss with post-lingual onset. Herein, we describe a male neonate from an ethnic Han Chinese family who presented with congenital deafness. METHODS: The proband and the family members were subjected to comprehensively hearing screen. Genetic testing was carried out using whole-exome sequencing (WES). The result was verified by Sanger sequencing. Functional characterization of the identified variant was completed by reverse transcription PCR (RT-PCR), Sanger sequencing, and fluorogenic quantitative PCR (qPCR). RESULTS: The proband was diagnosed with progressive sensorineural hearing loss. The proband's mother showed normal hearing at present. The proband's maternal grandmother exhibited mild HL since the age of 50. Using whole-exome sequencing (WES), we identified a donor splice-site variant (NM_014332.2: c.132 + 1G>A) in the SMPX gene in the proband. The mother and maternal grandmother were both carriers, which suggested a X-linked inheritance of the condition in the family. RT-PCR and Sanger sequencing revealed that four alternative splice pairs within intron 3 have led to four aberrant RNAs transcripts, including two non-canonical splice-pairs (GC-AG and CT-AG). The variant generated a novel frameshift variant, creating a premature termination codon (PTC) upstream of a newly formed splice site (p.Met45Glyfs*16). SMPX mRNA expression assay showed that the PTC has caused degradation of mRNA via nonsense-mediated mRNA decay (NMD). CONCLUSION: This is the first study to report a SMPX (DFNX4) splicing variant in a Chinese family. These findings, especially congenital deafness, contributed to existing knowledge regarding the genotypic and phenotypic spectrum of SMPX-associated hearing loss.


Assuntos
Sequenciamento do Exoma/métodos , Doenças Genéticas Ligadas ao Cromossomo X/etiologia , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/etiologia , Proteínas Musculares/genética , Polimorfismo de Nucleotídeo Único , Sítios de Splice de RNA , Splicing de RNA/genética , Criança , Pré-Escolar , Feminino , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Perda Auditiva Neurossensorial/patologia , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Prognóstico
18.
J Genet ; 982019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30945692

RESUMO

A parental diagnosis was performed for an unborn foetus of a healthy couple, who was due for ultrasound detection of multiple malformations and abnormal amniotic fluid karyotypes. For an accurate diagnosis, routine G-banding analysis and next generation sequencing (NGS) were carried out. Finally, conventional cytogenetic analysis suggested that the foetus had a karyotype of47,XX,+mar[52]/46,XN, meanwhile NGS also revealed a partial tetrasomy of 27.84Mb from 4q26-q31.21 (117,385,735-145,225,759), and G-banding analysis excluded the couple to have carried the 4q26-q31.21 duplication. We have identified a de novo mosaic small supernumerary marker chromosomes (sSMC) derived from 4q26-q31.21 in a foetus with hemivertebra, polydactyly, abnormal ears, and heart and ventricular septal defect.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Cromossomos Humanos Par 4/genética , Feto/patologia , Marcadores Genéticos , Diagnóstico Pré-Natal , Tetrassomia , Adulto , Análise Citogenética , Feminino , Feto/metabolismo , Humanos , Masculino , Mosaicismo , Gravidez
19.
Expert Rev Mol Diagn ; 19(2): 189-196, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30582381

RESUMO

OBJECTIVES: This study was aimed to report the clinical characteristics of fetal chromosomal aneuploidy diseases using noninvasive prenatal testing (NIPT) in twin pregnancies and analyze the results in terms of chorionicity, conception, and fetal fraction. METHODS: A total of 1160 women with twin pregnancies were recruited from 1 October 2015, to 1 August 2017. Next-generation sequencing technology was used to detect fetal aneuploidies, such as trisomy 21, trisomy 18, trisomy 13 and trisomy X. RESULTS: Aneuploidy was detected using NIPT in 26 fetuses, among which 18 fetal aneuploidies occurred in only one fetus of the twins. The rate of aneuploidy was 1.3% for dichorionic diamniotic twins and 0.5% for monochorionic diamniotic twins, respectively. The rate of aneuploidy was 1.2% for spontaneous pregnancy group and 1.1% for assisted reproductive technologies group. CONCLUSION: In this study, detection of trisomy 21, trisomy 18, trisomy 13, and X abnormality in twin pregnancies was confirmed to be accurate. The aneuploidies mostly occurred in only one fetus of the twins, and trisomy 21 was the most common type. The prenatal diagnostic standard for NIPT in singleton pregnancies could perform well in twin pregnancies, which means NIPT can be popularized as routine prenatal screening in twin pregnancies.


Assuntos
Síndrome de Down , Doenças Fetais , Gravidez de Gêmeos , Diagnóstico Pré-Natal , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18 , Trissomia , Cromossomos Humanos X/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Feminino , Doenças Fetais/diagnóstico , Doenças Fetais/genética , Testes Genéticos , Humanos , Gravidez , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Trissomia/diagnóstico , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13/diagnóstico , Síndrome da Trissomia do Cromossomo 13/genética , Síndrome da Trissomía do Cromossomo 18/diagnóstico , Síndrome da Trissomía do Cromossomo 18/genética
20.
BMC Pregnancy Childbirth ; 18(1): 443, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30428855

RESUMO

BACKGROUND: Monochorionic diamniotic (MCDA) twin pregnancies are at higher risk of adverse outcomes and complications, which are attributed to the influence of placental morphology in MCDA twins. Monitoring of placental function is an important index for clinical decisions. The aim of our study was to evaluate the placental blood flow estimated using three-dimensional power Doppler (3D-PD) ultrasound and the vascular indices distribution with gestational age (GA) in normal MCDA twin pregnancies. METHODS: One hundred four MCDA twin pregnancies and 106 singleton pregnancies (GA range, 14-32 weeks) were included in this prospective study. 3D-PD volume data of each fetus was obtained separately from the placenta at the site of umbilical cord insertion. We analyzed the volume data using sonobiopsy technique. The placental vascularization index (VI), flow index (FI) and vascularizationflow index (VFI), were auto-calculated. The means and standard deviation values of three vascular indices per fetus were calculated and regression analysis of the vascular indices as a function of GA was performed in twin pregnancies. The vascular indices of twin and singleton pregnancies were compared using independent t-test. RESULTS: There were no significant differences in VI, FI or VFI among the fetuses of twins (p > 0.05). These vascular indices increased over the course of pregnancy (p < 0.05). We obtained the regression equations for the indices as a function of GA in days: VI = exp. (4.369-28.533/GA) (R2 = 0.699, p < 0.05), FI = exp. (3.916-13.003/GA) (R2 = 0.511, p < 0.05), and VFI = exp. (3.577-37.468/GA) (R2 = 0.675, p < 0.05). There were no significant differences in three vascular indices between MCDA twin and singleton groups (p > 0.05). CONCLUSIONS: 3D-PD placental data using sonobiopsy technique could reflect the placental blood flow of each twin, which could be applied to the study of placental perfusion in MCDA twin pregnancies. This study also presented the vascular indices distribution with GA in normal twin pregnancies, which might be useful for early detection of MCDA complications.


Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Imageamento Tridimensional/métodos , Placenta/irrigação sanguínea , Gravidez de Gêmeos , Ultrassonografia Doppler/métodos , Ultrassonografia Pré-Natal/métodos , Adulto , Feminino , Humanos , Gravidez , Estudos Prospectivos , Gêmeos Monozigóticos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...