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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(2): 127-130, 2021 Feb 10.
Artigo em Chinês | MEDLINE | ID: mdl-33565063

RESUMO

OBJECTIVE: To analyze the clinical phenotype and genetic characterization of a child with early infantile epileptic encephalopathy. METHODS: The proband was subjected to history taking and was diagnosed based on his clinical manifestation, magnetic resonance imaging (MRI) and whole exome sequencing (WES). Sanger sequencing was carried out to determine the origin of pathogenic variant. RESULTS: The proband unconsciously tilts his head to one side with squint, which revealed an abnormal discharge. MRI indicated suspicious abnormal signal shadow in the left posterior frontal cortex in addition with inflammation signs in the right maxillary sinus and ethmoid sinus. WES revealed that the proband has carried a heterozygous c.5789G>A variant in the CACNAIA gene. The result of Sanger sequencing was in keeping with that of WES. Neither of his parents has carried the same variant. CONCLUSION: The heterozygous c.5789G>A variant of the CACNAIA gene probably underlay the early infantile epileptic encephalopathy 42 in the proband, which has a de novo origin.


Assuntos
Canais de Cálcio/genética , Testes Genéticos , Espasmos Infantis/genética , Heterozigoto , Humanos , Lactente , Mutação , Espasmos Infantis/diagnóstico , Sequenciamento Completo do Exoma
2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(1): 67-70, 2021 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-33423262

RESUMO

OBJECTIVE: To carry out genetic testing for an abortus suspected with Cornelia de Lange syndrome (CdLS). METHODS: History of gestation and the family was taken. Combined with prenatal ultrasonography and the phenotype of the abortus, a diagnosis was made for the proband. Fetal tissue and peripheral blood samples of its parents were collected for the extraction of genomic DNA. Whole exome sequencing was carried out to detect mutations related to the phenotype. Suspected mutations were verified in the parents through Sanger sequencing. RESULTS: Prenatal ultrasound found that the forearms and hands of the fetus were anomalous, in addition with poorly formed vermis cerebellum, slight micrognathia, and increased echo of bilateral renal parenchyma. Examination of the abortus has noted upper limb and facial malformations. Whole exome sequencing revealed that the fetus carried a heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene. The same mutation was not found in either parent. CONCLUSION: The heterozygous c.2118delG (p.Lys706fs) frameshift mutation of the NIPBL gene probably underlies the CdLS in the fetus. Above finding has provided a basis for the genetic counseling for the family.


Assuntos
Síndrome de Cornélia de Lange , Mutação , Proteínas de Ciclo Celular/genética , Análise Mutacional de DNA , Síndrome de Cornélia de Lange/genética , Síndrome de Cornélia de Lange/patologia , Feminino , Feto , Humanos , Masculino , Fenótipo , Gravidez , Sequenciamento Completo do Exoma
3.
Front Genet ; 11: 594078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193741

RESUMO

Multiple congenital anomalies-hypotonia-seizures syndrome 1 (MCAHS1) caused by phosphatidylinositol-glycan biosynthesis class N (PIGN) mutations is an autosomal recessive disease involving many systems of the body, such as the urogenital, cardiovascular, gastrointestinal, and central nervous systems. Here, compound heterozygous variants NM_012327.6:c.2427-2A > G and c.963G > A in PIGN were identified in a Chinese proband with MCAHS1. The features of the MCAHS1 family proband were evaluated to understand the mechanism of the PIGN mutation leading to the occurrence of MCAHS1. Ultrasound was conducted to examine the fetus, and his clinical manifestations were evaluated. Genetic testing was performed by whole-exome sequencing and the results were verified by Sanger sequencing of the proband and his parents. Reverse transcription-polymerase chain reaction was performed, and the products were subjected to Sanger sequencing. Quantitative PCR (Q-PCR) was conducted to compare gene expression between the patient and wild-type subjects. The compound heterozygous mutation NM_012327.6:c.2427-2A > G and c.963G > A was identified by whole-exome sequencing and was confirmed by Sanger sequencing. The NM_012327.6:c.2427-2A > G mutation led to skipping of exon 26, which resulted in a low expression level of the gene, as measured by Q-PCR. These findings provided a basis for genetic counseling and reproduction guidance in this family. Phenotype-genotype correlations may be defined by an expanded array of mutations.

4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(10): 1226-1230, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33198869

RESUMO

OBJECTIVE: To investigate the value of growth differentiation factor-15 (GDF-15) and extravascular lung water index (EVLWI) in severity grading and prognosis prediction of patients with acute respiratory distress syndrome (ARDS). METHODS: Patients with ARDS aged 18-75 years admitted to the department of respiratory intensive care unit (RICU) of Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2019 to February 2020 were enrolled. All patients were treated with conventional therapies such as mechanical ventilation, anti-infection, stabilization of water, electrolytes and acid-base environment, blood purification and nutritional support according to their conditions. Besides, the pulse-indicated continuous cardiac output (PiCCO) was performed after admission to the department, and EVLWI before treatment and at 24, 48 and 72 hours of treatment were recorded. Serum GDF-15 level was measured by enzyme linked immunosorbent assay (ELISA) during the same period. Patients were classified as mild, moderate, and severe degree according to the 2012 Berlin Definition of ARDS, and EVLWI and GDF-15 levels in patients with different disease levels before and after treatment were compared. In addition, the length of intensive care unit (ICU) stay, ICU mortality, and 28-day mortality of patients with different GDF-15 or EVLWI levels were analyzed comparatively, with the GDF-15 3 458 ng/L and EVLWI 15 mL/kg as the cut point. RESULTS: A total of 82 patients with ARDS were enrolled, including 22 patients with mild ARDS, 28 patients with moderate ARDS, and 32 patients with severe ARDS. The GDF-15 and EVLWI levels in patients with moderate and severe ARDS at each time point before and after treatment were higher than those in patients with mild ARDS. Both GDF-15 and EVLWI levels in patients with severe ARDS were higher than those in the patients with moderate ARDS. The differences were statistically significant at all the time points except for the difference of GDF-15 levels at 24 hours after treatment (ng/L: 3 900.41±546.43 vs. 3 695.66±604.73, P > 0.05). [GDF-15 (ng/L): 3 786.11±441.45 vs. 3 106.83±605.09 before treatment, 3 895.48±558.96 vs. 3 333.29±559.66 at 48 hours, 3 397.33±539.56 vs. 3 047.53±499.57 at 72 hours; EVLWI (mL/kg): 19.06±1.91 vs. 14.31±1.50 before treatment, 18.56±2.23 vs. 13.26±1.69 at 24 hours, 17.23±1.76 vs. 12.45±1.36 at 48 hours, 15.47±1.81 vs. 11.13±2.19 at 72 hours, all P < 0.05]. According to the cut-off value, there were 23 patients with GDF-15 ≥ 3 458 ng/L and GDF-15 < 3 458 ng/L respectively and there were 23 patients with EVLWI ≥ 15 mL/kg and EVLWI < 15 mL/kg respectively. The length of ICU stay and 28-day mortality in patients with high GDF-15 were significantly higher than those in patients with low GDF-15 [length of ICU stay (days): 21.22±2.69 vs. 15.37±3.14, 28-day mortality: 56.5% vs. 21.7%, both P < 0.05]. The length of ICU stay and 28-day mortality in patients with high EVLWI were also significantly higher than those in patients with low EVLWI [length of ICU stay (days): 18.45±2.61 vs. 14.98±2.75, 28-day mortality: 47.8% vs. 17.4%, both P < 0.05]. CONCLUSIONS: To some extent, GDF-15 and EVLWI levels reflect the severity of patients with ARDS, and high GDF-15 and EVLWI levels are significantly associated with poor prognosis in patients with ARDS.


Assuntos
Fator 15 de Diferenciação de Crescimento/análise , Adolescente , Adulto , Idoso , Débito Cardíaco , Água Extravascular Pulmonar , Humanos , Pessoa de Meia-Idade , Prognóstico , Índice de Gravidade de Doença , Adulto Jovem
5.
Front Genet ; 11: 569284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33110423

RESUMO

Autosomal dominant non-syndromic hearing loss (ADNSHL) has a broad phenotypic spectrum which includes bilateral, symmetrical, and high-frequency sensorineural hearing loss, that eventually progresses into hearing loss at all frequencies. Several genetic variations have been identified as causal factors underlying deafness, autosomal dominant 5 (DFNA5) gene-related hearing loss. Here, we report a novel mutation (c.991-1G > C) in DFNA5, which co-segregated with late-onset ADNSHL in a Chinese family and was identified via exome sequencing and Sanger sequencing of DNA from peripheral blood of the family members. Further sequencing of cDNA derived from peripheral blood mRNA revealed that the c.991-1G >C mutation led to the skipping of exon 8, which is a known pathogenic mechanism for DFNA5-related hearing loss.

6.
Cells ; 9(10)2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33036231

RESUMO

Blood extracellular vesicles (BEVs) carry bioactive cargo (proteins, genetic materials, lipids, licit, and illicit drugs) that regulate diverse functions in target cells. The cannabinoid drug delta-9-tetrahydrocannabinol (THC) is FDA approved for the treatment of anorexia and weight loss in people living with HIV. However, the effect of THC on BEV characteristics in the setting of HIV/SIV infection needs to be determined. Here, we used the SIV-infected rhesus macaque model of AIDS to evaluate the longitudinal effects of THC (THC/SIV) or vehicle (VEH/SIV) treatment in HIV/SIV infection on the properties of BEVs. While BEV concentrations increased longitudinally (pre-SIV (0), 30, and 150 days post-SIV infection (DPI)) in VEH/SIV macaques, the opposite trend was observed with THC/SIV macaques. SIV infection altered BEV membrane properties and cargo composition late in infection, since i) the electrostatic surface properties (zeta potential, ζ potential) showed that RM BEVs carried negative surface charge, but at 150 DPI, SIV infection significantly changed BEV ζ potential; ii) BEVs from the VEH/SIV group altered tetraspanin CD9 and CD81 levels compared to the THC/SIV group. Furthermore, VEH/SIV and THC/SIV BEVs mediated divergent changes in monocyte gene expression, morphometrics, signaling, and function. These include altered tetraspanin and integrin ß1 expression; altered levels and distribution of polymerized actin, FAK/pY397 FAK, pERK1/2, cleaved caspase 3, proapoptotic Bid and truncated tBid; and altered adhesion of monocytes to collagen I. These data indicate that HIV/SIV infection and THC treatment result in the release of bioactive BEVs with potential to induce distinct structural adaptations and signaling cues to instruct divergent cellular responses to infection.

7.
Cancers (Basel) ; 12(9)2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32872253

RESUMO

BST-2 is a novel driver of cancer progression whose expression confers oncogenic properties to breast cancer cells. As such, targeting BST-2 in tumors may be an effective therapeutic approach against breast cancer. Here, we sought to develop potent cytotoxic anti-cancer agent using the second-generation BST-2-based anti-adhesion peptide, B18, as backbone. To this end, we designed a series of five B18-derived peptidomimetics. Among these, B18L, a cationic amphiphilic α-helical peptidomimetic, was selected as the drug lead because it displayed superior anti-cancer activity against both drug-resistant and drug-sensitive cancer cells, with minimal toxicity on normal cells. Probing mechanism of action using molecular dynamics simulations, biochemical and membrane biophysics studies, we observed that B18L binds BST-2 and possesses membranolytic characteristics. Furthermore, molecular biology studies show that B18L dysregulates cancer signaling pathways resulting in decreased Src and Erk1/2 phosphorylation, increased expression of pro-apoptotic Bcl2 proteins, caspase 3 cleavage products, as well as processing of the caspase substrate, poly (ADP-ribose) polymerase-1 (PARP-1), to the characteristic apoptotic fragment. These data indicate that through the coordinated regulation of membrane, mitochondrial and signaling events, B18L executes cancer cell death and thus has the potential to be developed into a potent and selective anti-cancer compound.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(9): 929-933, 2020 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-32820501

RESUMO

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic diagnosis. METHODS: A male patient with achondroplasia due to a de novo FGFR3 variant was subjected to single sperm isolation and sequencing. Twenty single sperm samples were isolated by mechanical immobilization, and their whole genome was amplified. PCR primers were designed for the variant site and 25 flanking single nucleotide polymorphism (SNP) loci, and the PCR products were sequenced to determine the chromosomal haplotype which did not harbor the pathogenic variant. Biopsy samples of 12 embryonic trophoblasts were taken. Following whole genome amplification, high-throughput sequencing was carried out to detect the carrier status of the embryos. Wild type blastocysts were selected for transplantation. Amniotic fluid samples were taken at 19 weeks of gestation to confirm the status of the fetus. RESULTS: Eight SNP were selected by single sperm sequencing, with which the haplotypes were successfully constructed. Preimplantation genetic testing indicated that 5 embryos have carried the pathogenic variant and 7 did not. Testing of amniotic fluid sample during the second trimester of pregnancy confirmed that the fetus did not carry the FGFR3 gene c.1138G>A variant. CONCLUSION: For male patients carrying de novo pathogenic variants, SNP sites can be selected through single sperm sequencing, and haplotypes can be constructed by linkage analysis for preimplantation genetic diagnosis.


Assuntos
Acondroplasia/diagnóstico , Testes Genéticos , Diagnóstico Pré-Implantação , Análise de Célula Única , Espermatozoides , Acondroplasia/genética , Feminino , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Gravidez , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética
9.
Int J Mol Sci ; 21(15)2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32731547

RESUMO

Acellular particles (extracellular vesicles and membraneless condensates) have important research, drug discovery, and therapeutic implications. However, their isolation and retrieval have faced enormous challenges, impeding their use. Here, a novel size-guided particle purification liquid chromatography (PPLC) is integrated into a turbidimetry-enabled system for dye-free isolation, online characterization, and retrieval of intact acellular particles from biofluids. The chromatographic separation of particles from different biofluids-semen, blood, urine, milk, and cell culture supernatants-is achieved using a first-in-class gradient size exclusion column (gSEC). Purified particles are collected using a fraction collector. Online UV-Vis monitoring reveals biofluid-dependent particle spectral differences, with semen being the most complex. Turbidimetry provides the accurate physical characterization of seminal particle (Sp) lipid contents, sizes, and concentrations, validated by a nanoparticle tracking analysis, transmission electron microscopy, and naphthopyrene assay. Furthermore, different fractions of purified Sps contain distinct DNA, RNA species, and protein compositions. The integration of Sp physical and compositional properties identifies two archetypal membrane-encased seminal extracellular vesicles (SEV)-notably SEV large (SEVL), SEV small (SEVS), and a novel nonarchetypalµµembraneless Sps, herein named membraneless condensates (MCs). This study demonstrates a comprehensive yet affordable platform for isolating, collecting, and analyzing acellular particles to facilitate extracellular particle research and applications in drug delivery and therapeutics. Ongoing efforts focus on increased resolution by tailoring bead/column chemistry for each biofluid type.

10.
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 Completo do Exoma
11.
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.

12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(7): 767-770, 2020 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-32619261

RESUMO

OBJECTIVE: To explore the genetic basis for fetus with short limbs detected by prenatal ultrasonography. METHODS: Results of clinical imaging of the fetus was collected. Amniotic fluid sample was collected through amniocentesis for the extraction of fetal DNA. Whole exome sequencing was carried out to detect variants related to the clinical phenotypes. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound showed that the fetus had short limbs but no other abnormality. Whole exome sequencing has identified that the fetus carried two heterozygous pathogenic variants c.484G>T and c.1436dupA of the SLC26A2 gene, for which its mother and father were heterozygous carriers, respectively. CONCLUSION: The fetus was diagnosed with atelosteogenesis type 2 by combined prenatal ultrasonography and whole exome sequencing, which may be attributed to the compound heterozygous variants of the SLC26A2 gene. Above findings provided evidence for the diagnosis of the fetus and genetic counseling.


Assuntos
Osteocondrodisplasias , Feminino , Feto/diagnóstico por imagem , Humanos , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Sequenciamento Completo do Exoma
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(6): 629-632, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32472539

RESUMO

OBJECTIVE: To report on echocardiographic finding and genetic testing of three fetuses with cardiac rhabdomyoma. METHODS: Clinical data of the three fetuses was collected. High-throughput sequencing was carried out to analyze the whole exomes of the three fetuses. Suspected variants were confirmed by Sanger sequencing. RESULTS: Multiple hyperechoic masses were found in both ventricles of the three fetuses, suggesting the presence of fetal cardiac rhabdomyoma. Genetic testing revealed that fetus 1 carried a heterozygous c.740G>A (p.W247*) variant of the TSC1 gene, fetus 2 carried a previously known heterozygous c.3352C>T (p.Q1118*) variant of the TSC2 gene. Fetus 3 carried a previously known heterozygous c.1579C>T (p.Q527*) variant of the TSC1 gene. None of their parents carried the same variant. Literature review has identified 109 fetuses with relatively complete data. Cardiac rhabdomyomas in ventricles and ventricular septum was reported in 89, and multiple cardiac rhabdomyoma was reported in 79. Out of the 94 cases who underwent genetic testing, 74 have carried variants of the TSC1 or TSC2 genes. CONCLUSION: Fetal cardiac rhabdomyoma may present as multiple hyperechoic intraventricular masses. Most of them are associated with other manifestation of tuberous sclerosis. Such cases may warrant prenatal genetic testing.


Assuntos
Doenças Fetais , Neoplasias Cardíacas , Rabdomioma , Feminino , Testes Genéticos , Humanos , Gravidez , Esclerose Tuberosa
14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(5): 514-518, 2020 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-32335875

RESUMO

OBJECTIVE: To analyze the clinical phenotype of six pedigrees affected with osteogenesis imperfecta and their genetic basis. METHODS: Peripheral blood or abortic tissues of the six pedigrees were collected for the extraction of genomic DNA. Next generation sequencing (NGS) was carried out to detect pathological variants in the genome. Sanger sequencing was used for validating suspected variant among the six pedigrees and 100 healthy controls. RESULTS: In pedigree 1, the proband and his daughter both carried a heterozygous c.1976G>C variant of COL1A1. The probands in pedigrees 2 to 6 respectively carried heterozygous variants of c.2224G>A of COL1A2, c.2533G>A of COL1A1, c.2845G>A of COL1A2, c.2532_2540del of COL1A1, and c.1847G>A of COL1A2. The same variants were not detected in their parents and the 100 healthy controls. CONCLUSION: Variants of COL1A1/2 gene probably underlie the pathogenesis for osteogenesis imperfecta in these pedigrees. Discovery of the nevol variants has enriched the spectrum of COL1A1/2 gene variants and facilitated genetic counseling and prenatal diagnosis for the affected pedigrees.


Assuntos
Colágeno Tipo I , Variação Genética , Genótipo , Osteogênese Imperfeita , Fenótipo , Colágeno Tipo I/genética , Feminino , Humanos , Masculino , Mutação , Osteogênese Imperfeita/genética , Linhagem , Gravidez
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(5): 547-550, 2020 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-32335883

RESUMO

OBJECTIVE: To analyze the clinical features and pathogenesis of a fetus with holoprosencephaly. METHODS: The findings of prenatal ultrasonography was reviewed. Following elective abortion, whole exome sequencing (WES) was carried out to identify potential pathogenic variant. Copy number variants (CNVs) of the abortus and its parents were detected by low-depth high-throughput sequencing. The parents were also analyzed by chromosomal karyotyping. RESULTS: Prenatal ultrasound suggested that the fetus had holoprosencephaly. WES revealed that it had approximately 33 Mb deletion at chromosome 13 involving ZIC2, a haploid dose sensitive gene. The results of low-depth high-throughput sequencing confirmed that the fetus carried a de novo 32.32 Mb deletion at 13q31.1-34. Karyotyping analysis has excluded gross chromosomal aberration in both parents. CONCLUSION: The fetus was diagnosed with holoprosencephaly, which may be attributable to the 13q31.1-34 deletion involving the ZIC2 gene.


Assuntos
Holoprosencefalia , Deleção de Sequência , Adulto , Cromossomos Humanos Par 13/genética , Feminino , Feto , Testes Genéticos , Holoprosencefalia/diagnóstico por imagem , Holoprosencefalia/genética , Holoprosencefalia/patologia , Humanos , Cariotipagem , Masculino , Proteínas Nucleares/genética , Gravidez , Diagnóstico Pré-Natal , Fatores de Transcrição/genética , Ultrassonografia Pré-Natal , Sequenciamento Completo do Exoma
16.
Molecules ; 25(5)2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32155736

RESUMO

Inhibition of cancer cell adhesion is an effective approach to killing adherent cancer cells. B49 and its analog B49Mod1 peptides, derived from the extracellular domain (ECD) of bone marrow stromal antigen 2 (BST-2), display anti-adhesion activity on breast cancer cells. However, the minimal sequence required for this anti-adhesion activity is unknown. Here, we further characterized the anti-adhesion activity of B49Mod1. We show that the anti-adhesion activity of B49Mod1 may require cysteine-linked disulfide bond and that the peptide is susceptible to proteolytic deactivation. Using structure-activity relationship studies, we identified an 18-Mer sequence (B18) as the minimal peptide sequence mediating the anti-adhesion activity of B49Mod1. Atomistic molecular dynamic (MD) simulations reveal that B18 forms a stable complex with the ECD of BST-2 in aqueous solution. MD simulations further reveal that B18 may cause membrane defects that facilitates peptide translocation across the bilayer. Placement of four B18 chains as a transmembrane bundle results in water channel formation, indicating that B18 may impair membrane integrity and form pores. We hereby identify B18 as the minimal peptide sequence required for the anti-adhesion activity of B49Mod1 and provide atomistic insight into the interaction of B18 with BST-2 and the cell membrane.

17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 431-433, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219829

RESUMO

OBJECTIVE: To detect potential variants in a family affected with Usher syndrome type I, and analyze its genotype-phenotype correlation. METHODS: Clinical data of the family was collected. Potential variants in the proband were detected by high-throughput sequencing. Suspected variants were verified by Sanger sequencing. RESULTS: The proband developed night blindness at 10 year old, in addition with bilateral cataract and retinal degeneration. Hearing loss occurred along with increase of age. High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene, namely c.2694+2T>G and c.6028G>A. Her sister carried the same variants with similar clinical phenotypes. Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal. CONCLUSION: The clinical features and genetic variants were delineated in this family with Usher syndrome type I. The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.


Assuntos
Genótipo , Fenótipo , Síndromes de Usher , Criança , Feminino , Variação Genética , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Miosina VIIa/genética , Cegueira Noturna/etiologia , Linhagem , Síndromes de Usher/genética , Síndromes de Usher/patologia
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 462-466, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219838

RESUMO

OBJECTIVE: To analyze the clinical feature of a fetus with split hand-foot malformation (SHFM) and to explore its etiology. METHODS: Ultrasonographic finding of the fetus and X-ray examination of the abortus were reviewed. Genomic copy number variations (CNVs) of the fetus was analyzed by next-generation sequencing (NGS). Its parents were subjected to chromosomal karyotyping, NGS and fluorescence in situ hybridization (FISH) assays. Real-time fluorescence quantitative PCR was used to measure the expression of genes from the region containing abnormal CNVs. RESULTS: Ultrasonography and X-ray revealed that the right hand and both feet of the fetus were in a V-shape, which was suggestive of SFHM. The results of NGS revealed that the fetus has carried a 0.36 Mb deletion at 7q21.3 region. FISH and NGS analysis of both parents were normal. Real-time fluorescence quantitative PCR confirmed that the fetus carried a single copy of DYNC1I1 gene, while the copy numbers of SEM1, DLX5 and DLX6 genes were normal. CONCLUSION: The 7q21.3 microdeletion probably underlies the SHFM of the fetus, which has a de novo origin.


Assuntos
Cromossomos Humanos Par 7/genética , Dineínas do Citoplasma/genética , Deformidades Congênitas dos Membros/genética , Deleção Cromossômica , Variações do Número de Cópias de DNA , Feto , Humanos , Hibridização in Situ Fluorescente , Cariotipagem
19.
Chin Med J (Engl) ; 133(1): 17-24, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31923100

RESUMO

BACKGROUND: Blood glucose control is closely related to type 2 diabetes mellitus (T2DM) prognosis. This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network (EN) with a machine-learning algorithm to predict glycemic control. METHODS: Basic information, biochemical indices, and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017. An EN regression was used to address variable collinearity. Then, three common machine learning algorithms (random forest [RF], support vector machine [SVM], and back propagation artificial neural network [BP-ANN]) were used to simulate and predict blood glucose status. Additionally, a stepwise logistic regression was performed to compare the machine learning models. RESULTS: The well-controlled blood glucose rate was 45.82% in North China. The multivariable analysis found that hypertension history, atherosclerotic cardiovascular disease history, exercise, and total cholesterol were protective factors in glycosylated hemoglobin (HbA1c) control, while central adiposity, family history, T2DM duration, complications, insulin dose, blood pressure, and hypertension were risk factors for elevated HbA1c. Before the dimensional reduction in the EN, the areas under the curve of RF, SVM, and BP were 0.73, 0.61, and 0.70, respectively, while these figures increased to 0.75, 0.72, and 0.72, respectively, after dimensional reduction. Moreover, the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models (the sensitivity and accuracy of logistic were 0.52 and 0.56; RF: 0.79, 0.70; SVM: 0.84, 0.73; BP-ANN: 0.78, 0.73, respectively). CONCLUSIONS: More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications. The EN and machine learning algorithms are alternative choices, in addition to the traditional logistic model, for building predictive models of blood glucose control in patients with T2DM.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobina A Glicada/metabolismo , Insulina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , China , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Mol Cell Proteomics ; 19(1): 78-100, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676584

RESUMO

Blood and semen are important body-fluids that carry exosomes for bioinformation transmission. Therefore, characterization of their proteomes is necessary for understanding body-fluid-specific physiologic and pathophysiologic functions. Using systematic multifactorial proteomic profiling, we characterized the proteomes of exosomes and exosome-free fractions from autologous blood and semen from three HIV-uninfected and three HIV-infected participants (total of 24 samples). We identified exosome-based protein signatures specific to blood and semen along with HIV-induced tissue-dependent proteomic perturbations. We validated our findings with samples from 16 additional donors and showed that unlike blood exosomes (BE), semen exosomes (SE) are enriched in clusterin. SE but not BE promote Protein·Nucleic acid binding and increase cell adhesion irrespective of HIV infection. This is the first comparative study of the proteome of autologous BE and SE. The proteins identified may be developed as biomarkers applicable to different fields of medicine, including reproduction and infectious diseases.


Assuntos
Sangue/metabolismo , Exossomos/metabolismo , Infecções por HIV/metabolismo , HIV-1/genética , Proteoma , Proteômica/métodos , Sêmen/metabolismo , Adulto , Biomarcadores/metabolismo , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mapas de Interação de Proteínas , RNA Viral/genética , Adulto Jovem
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