RESUMO
The only genus of the Francisellaceae family known to contain species pathogenic to mammals is Francisella, for which reported cases in the Southern Hemisphere have been limited to Australia. We describe severe necrotizing and inflammatory lesions and intralesional immunohistochemical identification of Francisella sp. lipopolysaccharide among aborted ovine fetuses in Uruguay.
Assuntos
Doenças dos Ovinos , Gravidez , Feminino , Humanos , Ovinos , Animais , Uruguai/epidemiologia , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/patologia , Aborto Animal/patologia , Carneiro Doméstico , Feto Abortado/patologiaRESUMO
The ARID1A gene is an infrequent cause of Coffin-Siris syndrome (CSS) and has been associated with severe to profound developmental delays and hypotonia in addition to characteristic craniofacial and digital findings. We present three fetuses and a male neonate with ventriculomegaly/hydrocephalus, absence of the corpus callosum (ACC), cerebellar hypoplasia, retinal dysplasia, lung lobulation defects, renal dysplasia, imperforate or anteriorly placed anus, thymus hypoplasia and a single umbilical artery. Facial anomalies included downslanting palpebral fissures, wide-spaced eyes, low-set and posteriorly rotated ears, a small jaw, widely spaced nipples and hypoplastic nails. All fetuses had heterozygous variants predicting premature protein truncation in ARID1A (c.4886dup:p.Val1630Cysfs*18; c.4860dup:p.Pro1621Thrfs*27; and c.175G>T:p.Glu59*) and the baby's microarray demonstrated mosaicism for a deletion at chromosome 1p36.11 (arr[GRCh37] 1p36.11(26,797,508_27,052,080)×1â¼2), that contained the first exon of ARID1A. Although malformations, in particular ACC, have been described with CSS caused by pathogenic variants in ARID1A, prenatal presentations associated with this gene are rare. Retinal dysplasia, lung lobulation defects and absent thymus were novel findings in association with ARID1A variants. Studies in cancer have demonstrated that pathogenic ARID1A variants hamper nuclear import of the protein and/or affect interaction with the subunits of SWI/SNF complex, resulting in dysregulation of the PI3K/AKT pathway and perturbed PTEN and PIKC3A signaling. As haploinsufficiency for PTEN and PIKC3A can be associated with ventriculomegaly/hydrocephalus, aberrant expression of these genes is a putative mechanism for the brain malformations demonstrated in patients with ARID1A variants.
Assuntos
Anormalidades Múltiplas/diagnóstico , Feto Abortado/patologia , Proteínas de Ligação a DNA/genética , Face/anormalidades , Deformidades Congênitas da Mão/diagnóstico , Deficiência Intelectual/diagnóstico , Micrognatismo/diagnóstico , Pescoço/anormalidades , Fenótipo , Fatores de Transcrição/genética , Anormalidades Múltiplas/genética , Adulto , Feminino , Deformidades Congênitas da Mão/genética , Humanos , Deficiência Intelectual/genética , Micrognatismo/genética , Mutação , Gravidez , Diagnóstico Pré-NatalRESUMO
The Forkhead transcription factor FOXG1 is a prerequisite for telencephalon development in mammals and is an essential factor controlling expansion of the dorsal telencephalon by promoting neuron and interneuron production. Heterozygous FOXG1 gene mutations cause FOXG1 syndrome characterized by severe intellectual disability, motor delay, dyskinetic movements and epilepsy. Neuroimaging studies in patients disclose constant features including microcephaly, corpus callosum dysgenesis and delayed myelination. Currently, investigative research on the underlying pathophysiology relies on mouse models only and indicates that de-repression of FOXG1 target genes may cause premature neuronal differentiation at the expense of the progenitor pool, patterning and migration defects with impaired formation of cortico-cortical projections. It remains an open question to which extent this recapitulates the neurodevelopmental pathophysiology in FOXG1-haploinsufficient patients. To close this gap, we performed neuropathological analyses in two foetal cases with FOXG1 premature stop codon mutations interrupted during the third trimester of the pregnancy for microcephaly and corpus callosum dysgenesis. In these foetuses, we observed cortical lamination defects and decreased neuronal density mainly affecting layers II, III and V that normally give rise to cortico-cortical and inter-hemispheric axonal projections. GABAergic interneurons were also reduced in number in the cortical plate and persisting germinative zones. Additionally, we observed more numerous PDGFRα-positive oligodendrocyte precursor cells and fewer Olig2-positive pre-oligodendrocytes compared to age-matched control brains, arguing for delayed production and differentiation of oligodendrocyte lineage leading to delayed myelination. These findings provide key insights into the human pathophysiology of FOXG1 syndrome.
Assuntos
Agenesia do Corpo Caloso/genética , Axônios/patologia , Fatores de Transcrição Forkhead/genética , Microcefalia/genética , Proteínas do Tecido Nervoso/genética , Transtornos do Neurodesenvolvimento/genética , Neurogênese , Oligodendroglia/patologia , Feto Abortado/metabolismo , Feto Abortado/patologia , Adulto , Agenesia do Corpo Caloso/patologia , Axônios/metabolismo , Encéfalo/embriologia , Encéfalo/metabolismo , Encéfalo/patologia , Códon sem Sentido , Feminino , Fatores de Transcrição Forkhead/metabolismo , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/patologia , Humanos , Interneurônios/metabolismo , Interneurônios/patologia , Microcefalia/patologia , Bainha de Mielina/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transtornos do Neurodesenvolvimento/patologia , Oligodendroglia/metabolismo , Linhagem , Gravidez , SíndromeRESUMO
RESEARCH QUESTION: Is the karyotype of the first clinical miscarriage in an infertile patient predictive of the outcome of the subsequent pregnancy? DESIGN: Retrospective cohort study of infertile patients undergoing manual vacuum aspiration with chromosome testing at the time of the first (index) clinical miscarriage with a genetic diagnosis and a subsequent pregnancy. Patients treated at two academic-affiliated fertility centres from 1999 to 2018 were included; those using preimplantation genetic testing for aneuploidy were excluded. Main outcome was live birth in the subsequent pregnancy. RESULTS: One hundred patients with euploid clinical miscarriage and 151 patients with aneuploid clinical miscarriage in the index pregnancy were included. Patients with euploid clinical miscarriage in the index pregnancy had a live birth rate of 63% in the subsequent pregnancy compared with 68% among patients with aneuploid clinical miscarriage (adjusted odds ratio [aOR] 0.75, 95% CI 0.47-1.39, P = 0.45, logistic regression model adjusting for age, parity, body mass index and mode of conception). In a multinomial logistic regression model with three outcomes (live birth, clinical miscarriage or biochemical miscarriage), euploid clinical miscarriage for the index pregnancy was associated with similar odds of clinical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage for the index pregnancy (32% versus 24%, respectively, aOR 1.49, 95% CI 0.83-2.70, P = 0.19). Euploid clinical miscarriage for the index pregnancy was not associated with likelihood of biochemical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage (5% versus 8%, respectively, aOR 0.46, 95% CI 0.14-1.55, P = 0.21). CONCLUSION: Prognosis after a first clinical miscarriage among infertile patients is equally favourable among patients with euploid and aneuploid karyotype, and independent of the karyotype of the pregnancy loss.
Assuntos
Feto Abortado/patologia , Aborto Espontâneo/patologia , Cariótipo , Adulto , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Adulto JovemRESUMO
Intrauterine transmission of the Chikungunya virus (CHIKV) during early pregnancy has rarely been reported, although vertical transmission has been observed in newborns. Here, we report four cases of spontaneous abortion in women who became infected with CHIKV between the 11th and 17th weeks of pregnancy. Laboratorial confirmation of the infection was conducted by RT-PCR on a urine sample for one case, and the other three were by detection of IgM anti-CHIKV antibodies. Hematoxylin and eosin (H&E) staining and an electron microscopy assay allowed us to find histopathological, such as inflammatory infiltrate in the decidua and chorionic villi, as well as areas of calcification, edema and the deposition of fibrinoid material, and ultrastructural changes, such as mitochondria with fewer cristae and ruptured membranes, endoplasmic reticulum with dilated cisterns, dispersed chromatin in the nuclei and the presence of an apoptotic body in case 1. In addition, by immunohistochemistry (IHC), we found a positivity for the anti-CHIKV antibody in cells of the endometrial glands, decidual cells, syncytiotrophoblasts, cytotrophoblasts, Hofbauer cells and decidual macrophages. Electron microscopy also helped in identifying virus-like particles in the aborted material with a diameter of 40-50 nm, which was consistent with the size of CHIKV particles in the literature. Our findings in this study suggest early maternal fetal transmission, adding more evidence on the role of CHIKV in fetal death.
Assuntos
Feto Abortado/patologia , Aborto Espontâneo/patologia , Aborto Espontâneo/virologia , Febre de Chikungunya/complicações , Transmissão Vertical de Doenças Infecciosas , Feto Abortado/virologia , Adulto , Anticorpos Antivirais/sangue , Febre de Chikungunya/virologia , Vírus Chikungunya/patogenicidade , Feminino , Técnicas Histológicas , Humanos , Imunoglobulina M/sangue , GravidezRESUMO
Bartsocas-Papas syndrome (BPS) is a rare autosomal recessive disorder characterized by popliteal pterygia, syndactyly, ankyloblepharon, filiform bands between the jaws, cleft lip and palate, and genital malformations. Most of the BPS cases reported to date are fatal either in the prenatal or neonatal period. Causative genetic defects of BPS were mapped on the RIPK4 gene encoding receptor-interacting serine/threonine kinase 4, which is critical for epidermal differentiation and development. RIPK4 variants are associated with a wide range of clinical features ranging from milder ectodermal dysplasia to severe BPS. Here, we evaluated a consanguineous Turkish family, who had two pregnancies with severe multiple malformations compatible with BPS phenotype. In order to identify the underlying genetic defect, direct sequencing of the coding region and exon-intron boundaries of RIPK4 was carried out. A homozygous transversion (c.481G>C) that leads to the substitution of a conserved aspartic acid to histidine (p.Asp161His) in the kinase domain of the protein was detected. Pathogenicity predictions, molecular modeling, and cell-based functional assays showed that Asp161 residue is required for the kinase activity of the protein, which indicates that the identified variant is responsible for the severe BPS phenotype in the family.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Anormalidades do Olho/genética , Dedos/anormalidades , Articulação do Joelho/anormalidades , Joelho/anormalidades , Deformidades Congênitas das Extremidades Inferiores/genética , Proteínas Serina-Treonina Quinases/genética , Anormalidades da Pele/genética , Sindactilia/genética , Anormalidades Urogenitais/genética , Anormalidades Múltiplas/epidemiologia , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/patologia , Feto Abortado/patologia , Fenda Labial/epidemiologia , Fenda Labial/patologia , Fissura Palatina/epidemiologia , Fissura Palatina/patologia , Exoma/genética , Anormalidades do Olho/epidemiologia , Anormalidades do Olho/patologia , Feminino , Dedos/patologia , Predisposição Genética para Doença , Homozigoto , Humanos , Recém-Nascido , Joelho/patologia , Articulação do Joelho/patologia , Deformidades Congênitas das Extremidades Inferiores/epidemiologia , Deformidades Congênitas das Extremidades Inferiores/patologia , Mutação/genética , Fosforilação , Gravidez , Anormalidades da Pele/epidemiologia , Anormalidades da Pele/patologia , Sindactilia/epidemiologia , Sindactilia/patologia , Anormalidades Urogenitais/epidemiologia , Anormalidades Urogenitais/patologiaRESUMO
Porcine circovirus 3 (PCV-3) has been widely detected in healthy and diseased pigs; among different pathologic conditions, the strongest evidence of association comes from reproductive disease cases. However, simple viral detection does not imply the causality of the clinical conditions. Detection of PCV-3 within lesions may provide stronger evidence of causality. Thus, this study aimed to assess the frequency of PCV-3 detection in tissues from fetuses/stillborn piglets in cases of reproductive problems in domestic swine, as well as the histopathologic assessment of fetal tissues. Fetuses or stillborn piglets from 53 cases of reproductive failure were collected and analyzed by PCV-3 qPCR. The presence of porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus 2 (PCV-2), and porcine parvovirus 1 (PPV1) was also checked. PCV-3 qPCR positive samples with a high viral load were tested by PCV-3 in situ hybridization (ISH), sequenced, and phylogenetically analyzed. PCV-3 DNA was detected in 18/53 (33.9%) reproductive failure cases and in 16 of them PCV-3 was the only pathogen found. PCV-2 DNA was found in 5/53 (9.4%), PRRSV RNA in 4/53 (7.5%) and PPV1 was not detected. Four out of the six PCV-3 qPCR-positive cases with Ct value <30 were positive when tested by ISH. In these samples, PCV-3 was detected within mild histopathologic lesions, such as arteritis and periarteritis in multiple tissues. The present work emphasizes the need to include PCV-3 as a potential causative agent of reproductive failure in swine.
Assuntos
Aborto Animal/virologia , Infecções por Circoviridae/veterinária , Circovirus/isolamento & purificação , Doenças dos Suínos/virologia , Feto Abortado/patologia , Feto Abortado/virologia , Aborto Animal/patologia , Animais , Animais Domésticos , Infecções por Circoviridae/patologia , Infecções por Circoviridae/virologia , Circovirus/classificação , Circovirus/genética , DNA Viral/genética , Feminino , Genoma Viral/genética , Filogenia , Gravidez , Natimorto/veterinária , Suínos , Doenças dos Suínos/patologia , Carga Viral , Vírus/classificação , Vírus/genética , Vírus/isolamento & purificaçãoRESUMO
Cenani Lenz syndrome is a rare autosomal recessive disorder associated with variable degree of limb malformations, dysmorphism, and renal agenesis. It is caused due to pathogenic variants in the LRP4 gene, which plays an important role in limb and renal development. Mutations in the APC gene have also been occasionally associated with CLS. The phenotypic spectrum ranges from mild to very severe perinatal lethal type depending on the type of variant. We report a pathogenic variant, c.2710 del T (p.Trp904GlyfsTer5) in theLRP4 gene, in a fetus with lethal Cenani Lenz syndrome with antenatal presentation of tetraphocomelia and symmetrical involvement of hands and feet.
Assuntos
Anormalidades Congênitas/genética , Nefropatias/congênito , Rim/anormalidades , Proteínas Relacionadas a Receptor de LDL/genética , Deformidades Congênitas dos Membros/genética , Sindactilia/genética , Feto Abortado/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Anormalidades Congênitas/mortalidade , Anormalidades Congênitas/patologia , Feminino , Genes Letais/genética , Predisposição Genética para Doença , Homozigoto , Humanos , Ilhas do Oceano Índico/epidemiologia , Rim/patologia , Nefropatias/genética , Nefropatias/mortalidade , Nefropatias/patologia , Deformidades Congênitas dos Membros/mortalidade , Deformidades Congênitas dos Membros/patologia , Masculino , Mutação/genética , Linhagem , Fenótipo , Gravidez , Sindactilia/mortalidade , Sindactilia/patologiaRESUMO
INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare placental lesion strongly associated with recurrent miscarriages and fetal losses. It requires histopathological diagnosis and can only be made after delivery of the products of conception (POC). We describe a case of CHI in a 41-yearold lady with a 16-year history of thirteen recurrent consecutive first trimester miscarriages. CASE REPORT: The patient is a 41-year-old lady who suffered first trimester miscarriages in all her thirteen pregnancies. The relevant clinical investigations revealed neither significant nor helpful findings in determining the cause of recurrent miscarriages. Histological findings in each except one of the submitted conceptual tissue showed similar features of histiocytic aggregates primarily within the intervillous spaces, a characteristic description of CHI. One of the samples showed degenerative changes. DISCUSSION: Practicing pathologists are not familiar with the histological features of CHI and this may be a potential pitfall in routine examination of POCs. Recognising this entity allows for accurate diagnosis and hence better management. The aetiology remains unclear, although an immunopathological basis are being explored.
Assuntos
Feto Abortado/patologia , Aborto Habitual/patologia , Doenças Placentárias/patologia , Adulto , Doença Crônica , Feminino , Histiocitose/patologia , Humanos , GravidezRESUMO
INTRODUCTION: Congenital disorders of glycosylation (CDG) are inborn errors of glycan metabolism with high clinical variability. Only a few antenatal cases have been described with CDG. Due to a lack of reliable biomarker, prenatal CDG diagnostics relies primarily on molecular studies. In the presence of variants of uncertain significance prenatal glycosylation studies are very challenging. CASE REPORT: A consanguineous couple had a history of second-trimester fetal demise with tetralogy of Fallot and skeletal dysplasia. In the consecutive pregnancy, the second trimester ultrasonography showed skeletal dysplasia, vermian hypoplasia, congenital heart defects, omphalocele and dysmorphic features. Prenatal chromosomal microarray revealed a large region of loss of heterozygosity. Demise occurred at 30 weeks. Fetal whole exome sequencing showed a novel homozygous likely pathogenic variant in ALG3 and a variant of uncertain significance in COG5. METHODS: Western blot was used to quantify ALG3, COG5, COG6, and the glycosylation markers ICAM-1 and LAMP2. RT-qPCR was used for ALG3 and COG5 expression in cultured amniocytes and compared to age matched controls. RESULTS: ALG3 and COG5 mRNA levels were normal. ICAM-1, LAMP2, ALG3 and COG5 levels were decreased in cultured amniocytes, suggesting the possible involvement of both genes in the complex phenotype. CONCLUSION: This is the first case of successful use of glycosylated biomarkers in amniocytes, providing further options of functional antenatal testing in CDG.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/genética , Defeitos Congênitos da Glicosilação/genética , Glicosilação , Manosiltransferases/genética , Feto Abortado/patologia , Aborto Espontâneo/genética , Amniocentese , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/patologia , Feminino , Humanos , Molécula 1 de Adesão Intercelular/genética , Proteína 2 de Membrana Associada ao Lisossomo/genética , Mutação/genética , Fenótipo , GravidezAssuntos
Anormalidades Múltiplas/veterinária , Edema/veterinária , Pneumopatias/veterinária , Pulmão/anormalidades , Anormalidades Múltiplas/genética , Feto Abortado/patologia , Animais , Bovinos , Cromossomos Humanos Par 20 , Edema/genética , Pneumopatias/genética , Mosaicismo/veterinária , TrissomiaRESUMO
Our communication presents a prenatally detected case with severe spinal defect detected in the first trimester of pregnancy, accompanied by a large skin-covered myelomeningocele but normal cranio-cerebral structural appearance.These findings suggest that in the first trimester, the extent of the spinal defect, the cerebrospinal fluid leakage to a large, but skin-covered, meningocele and fixation of the spinal cord at the lesion are not sufficient to determine downward hindbrain displacement and the development of secondary signs for open spina bifida.Therefore, we suggest a careful evaluation of the fetal cerebral features if a meningocele is detected. The presence of the skin covering the lesion may not be evident in the first trimester, but the absence of intracranial open spina bifida markers may indicate a 'closed' spinal defect, which generally associates a good neurological outcome. Also, studies aimed to investigate the accuracy of the intracranial features for open spina bifida detection should consider the possibility of 'closed' myelomeningoceles to avoid incorrect correlations.
Assuntos
Anormalidades Múltiplas/diagnóstico , Aborto Eugênico/métodos , Encéfalo/diagnóstico por imagem , Crânio/diagnóstico por imagem , Espinha Bífida Cística/diagnóstico , Ultrassonografia Pré-Natal/métodos , Feto Abortado/patologia , Adulto , Erros de Diagnóstico/prevenção & controle , Feminino , Feto/diagnóstico por imagem , Idade Gestacional , Humanos , Meningomielocele , Gravidez , Primeiro Trimestre da Gravidez , Cuidado Pré-Natal/métodosAssuntos
Fístula Arteriovenosa/genética , Endoglina/genética , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Telangiectasia Hemorrágica Hereditária/genética , Feto Abortado/patologia , Adulto , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/patologia , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/mortalidade , Malformações Arteriovenosas/fisiopatologia , Feminino , Humanos , Masculino , Mutação/genética , Artéria Pulmonar/patologia , Veias Pulmonares/patologia , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/patologiaRESUMO
Wnt signaling pathways, including the canonical Wnt/ß-catenin pathway, planar cell polarity pathway, and Wnt/Ca2+ signaling pathway, play important roles in neural development during embryonic stages. The DVL genes encode the hub proteins for Wnt signaling pathways. The mutations in DVL2 and DVL3 were identified from patients with neural tube defects (NTDs), but their functions in the pathogenesis of human neural diseases remain elusive. Here, we sequenced the coding regions of three DVL genes in 176 stillborn or miscarried fetuses with NTDs or Dandy-Walker malformation (DWM) and 480 adult controls from a Han Chinese population. Four rare mutations were identified: DVL1 p.R558H, DVL1 p.R606C, DVL2 p.R633W, and DVL3 p.R222Q. To assess the effect of these mutations on NTDs and DWM, various functional analyses such as luciferase reporter assay, stress fiber formation, and in vivo teratogenic assay were performed. The results showed that the DVL2 p.R633W mutation destabilized DVL2 protein and upregulated activities for all three Wnt signalings (Wnt/ß-catenin signaling, Wnt/planar cell polarity signaling, and Wnt/Ca2+ signaling) in mammalian cells. In contrast, DVL1 mutants (DVL1 p.R558H and DVL1 p.R606C) decreased canonical Wnt/ß-catenin signaling but increased the activity of Wnt/Ca2+ signaling, and DVL3 p.R222Q only decreased the activity of Wnt/Ca2+ signaling. We also found that only the DVL2 p.R633W mutant displayed more severe teratogenicity in zebrafish embryos than wild-type DVL2. Our study demonstrates that these four rare DVL mutations, especially DVL2 p.R633W, may contribute to human neural diseases such as NTDs and DWM by obstructing Wnt signaling pathways.
Assuntos
Síndrome de Dandy-Walker/genética , Proteínas Desgrenhadas/genética , Defeitos do Tubo Neural/genética , Feto Abortado/patologia , Animais , Polaridade Celular/genética , Síndrome de Dandy-Walker/patologia , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Mutação/genética , Defeitos do Tubo Neural/patologia , Ativação Transcricional/genética , Via de Sinalização Wnt , Peixe-Zebra/genéticaRESUMO
Leptospirosis is a globally distributed disease associated with reproductive failures in livestock; however, its pathogenesis has not been fully elucidated. Results from the present study indicate there is a presence of Leptospira sp. in organs and fluids of fetuses from ewes slaughtered in the semiarid region of Brazil. Twenty-nine fetuses from 23 ewes determined to be Leptospira sp.-positive using PCR were sampled (14 and 15 in dry and rainy seasons, respectively). Fetal samples of blood, central nervous system (CNS), lung, liver, spleen, stomach contents, peritoneal fluid, kidney, bladder, urine and reproductive system were collected. Diagnostic methods included the microscopic agglutination test (MAT), polymerase chain reaction (PCR) and bacterial isolation. Of the 29 fetuses, 24 (82.8 %) had at least one Leptospira sp.-positive organ or fluid, as determined using PCR, and of a total of 209 samples, 62 (29.7 %) contained leptospiral DNA. Of the 99 samples collected during the dry season, 42 (42.4 %) were positive, and of 110 samples collected during the rainy season, 20 (18.2 %) were positive (P = 0.0001). There was deoxyribonucleic acid (DNA) sequencing of three samples of kidney, CNS and liver, and in all of these, there was 99.3 % similarity with Leptospira interrogans. Leptospires were present in cultures of pooled samples from fetuses with deformities. Results indicate there is vertical (maternal-to-fetus) transmission which would represent an alternative transmission route for the spread of Leptospira sp. in ewes, suggesting molecular detection is essential in the investigation of leptospirosis in fetuses to identify animals that have been infected with this bacterium.
Assuntos
Clima Desértico , Transmissão Vertical de Doenças Infecciosas/veterinária , Leptospirose/transmissão , Prenhez , Doenças dos Ovinos , Feto Abortado/microbiologia , Feto Abortado/patologia , Testes de Aglutinação/veterinária , Animais , Líquidos Corporais/microbiologia , Brasil/epidemiologia , Feminino , Genitália Feminina/microbiologia , Genitália Feminina/patologia , Incidência , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Leptospira/classificação , Leptospira/genética , Leptospira/isolamento & purificação , Leptospirose/epidemiologia , Leptospirose/microbiologia , Leptospirose/patologia , Masculino , Reação em Cadeia da Polimerase/veterinária , Gravidez , Ovinos , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/microbiologia , Doenças dos Ovinos/patologia , Doenças dos Ovinos/transmissão , Sistema Urinário/microbiologia , Sistema Urinário/patologiaRESUMO
This study was carried out on seven flocks of ewes suffered from late abortion and neonatal mortality with the prevalence rate of infection reported as 13.95%. The blood and tissue samples were collected from the aborted ewes in several flocks of Duhok province, Kurdistan Region, Iraq. Serological analysis indicated that all the aborted ewes were confirmed positive for agglutination to Toxoplasma gondii (T. gondii)antibody. The investigation of the aborted fetuses showed the blood-stained fluid in the thoracic and abdominal cavity. Most of the aborted fetuses had also enlarged, congested, and friable livers and lungs. The placenta was swollen, reddish, and friable, and its cotyledons also spotted with whitish foci. T. gondii tachyzoites were also demonstrated in the placental sections of some aborted ewes. Severe congestion, necrosis, and infiltration of multinucleated cells were the most predominant histopathological changes of the aborted fetuses, as well as presented tissue cysts, tachyzoites, and bradyzoites in the liver, brain, heart, and lung. There were also several clusters of dark purple banana-shaped T. gondii tachyzoites within the brain and heart tissues in most of the examined aborted fetuses in different flocks. T. gondii tachyzoites were also detected from the peritoneal ascites of mice inoculated experimentally 12 days following the infection. Moreover, T. gondii tissue cysts were detected from the impression smears of the mice brains 32 days after the infection. Accordingly, the demonstration of T. gondii in Giemsa-stained impression smears associated with characteristic histopathological changes of different organs is a great fundamental method for the diagnosis of T. gondii in aborted cases.
Assuntos
Aborto Animal/epidemiologia , Doenças dos Ovinos/epidemiologia , Toxoplasmose Animal/epidemiologia , Feto Abortado/patologia , Aborto Animal/mortalidade , Aborto Animal/parasitologia , Animais , Animais Recém-Nascidos , Feminino , Incidência , Iraque/epidemiologia , Ovinos , Doenças dos Ovinos/mortalidade , Doenças dos Ovinos/parasitologia , Carneiro Doméstico , Toxoplasma/fisiologia , Toxoplasmose Animal/mortalidade , Toxoplasmose Animal/parasitologiaRESUMO
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 ExomaRESUMO
BACKGROUND: Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. METHODS: We report six cases of nemaline myopathy 8 which involves the c.1516A>C variant, from five unrelated families of non-consanguineous southern Chinese. The pre- and postnatal phenotypes of these cases were reviewed with emphasis on prenatal clinical features. Genetic testing for the founder mutation was performed on three patients with homozygous mutations. RESULTS: Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet. Two pregnancies were terminated. Four live-born patients had postnatal features typical of nemaline myopathy 8. The length of survival ranged from 49 days to 17 months, with respiratory failure and infections being the principal causes of death. Haplotype analysis in three patients with homozygous mutation showed a shared haplotype block of 1.1727 cM spanning over the c.1516A>C variant, suggesting it is a southern Chinese-specific founder mutation. CONCLUSION: Analysis of the KLHL40 c.1516A>C variant should be considered in prenatal diagnosis of Chinese pregnant patients with suspected congenital neuromuscular disorders or with significant family history of congenital myopathies.
Assuntos
Efeito Fundador , Proteínas Musculares/genética , Miopatias da Nemalina/genética , Feto Abortado/patologia , Adulto , China , Feminino , Haplótipos , Homozigoto , Humanos , Recém-Nascido , Miopatias da Nemalina/patologia , Fenótipo , Mutação PuntualRESUMO
OBJECTIVE: To describe the ultrasonographic, pathologic and molecular findings in a fetus with TAR syndrome, and to illustrate the contribution of chromosomal microarray analysis (CMA) to the etiological investigation of fetal upper limb reduction defects. CASE REPORT: A 35-year-old woman was referred for Genetic Counseling after pregnancy termination for severe upper limb bilateral phocomelia detected in the second trimester. Fetal autopsy showed severe shortening of the arms and forearms. The fetal skeletal survey confirmed the absence of the radii, ulnae and humeri. CMA revealed an interstitial deletion in 1q21 including the RBM8A gene. Subsequent Sanger sequencing of this gene identified a hypomorphic mutant allele, c.-21G > A, confirming the diagnosis of TAR syndrome. CONCLUSION: The differential diagnosis of upper limb defects is broad. Identification of their cause is essential for adequate genetic counseling including prognosis and recurrence risk estimation. CMA should be considered in fetuses with upper limb reduction defects, especially when the thumbs are present.
Assuntos
Síndrome Congênita de Insuficiência da Medula Óssea/diagnóstico , Ectromelia/diagnóstico , Trombocitopenia/diagnóstico , Deformidades Congênitas das Extremidades Superiores/diagnóstico , Feto Abortado/patologia , Adulto , Síndrome Congênita de Insuficiência da Medula Óssea/embriologia , Diagnóstico Diferencial , Ectromelia/embriologia , Ectromelia/genética , Feminino , Aconselhamento Genético , Humanos , Análise em Microsséries , Gravidez , Segundo Trimestre da Gravidez , Rádio (Anatomia)/embriologia , Trombocitopenia/congênito , Trombocitopenia/embriologia , Deformidades Congênitas das Extremidades Superiores/embriologia , Deformidades Congênitas das Extremidades Superiores/genéticaRESUMO
BACKGROUND: Syncytin-1 and syncytin-2 which are endogenous retroviral genes products play a great role in syncytialization during trophoblast differentiation in normal placental tissues. In aneuploidic placentas due to the low level of pregnancy-induced hormones an alteration was occurred in the syncytialization process, while in the presence of cytogenetically abnormal karyotype the effect of syncytin gene expression levels on syncytialization process and in occured to spontaneous abortions is not clear. To reveal this, we investigated in syncytin-1 and syncytin-2 genes expression levels of chromosomally abnormal and normal trophophoblastic tissues and we also discussed the effect of the syncytin gene expression levels to the occurense of the spontaneous abortion. MATERIAL AND METHODS: To each one of the trophoblastic cells; cultivation, harvesting, banding, and analysis were performed and the chromosomes were classified according to the presence of abnormality and normal XY constitution. To exclude the maternal decidual cell contamination, female karyotyped abortion materials were omitted in control group. The patient group consisted of thirty six placental tissues including trisomy 16 (n = 10), triploidy (n = 9), monosomy X (n = 9), trisomy 21 (n = 5) and trisomy 7 (n = 3). The control group was consisting twenty placental tissues with XY karyotypes. The some part of the dissected frozen trophoblastic cells were used for RNA isolation and were proceeded to the determination of the expression levels of syncytin-1 and syncytin-2 genes by single-step Real Time PCR. The cDNAs were obtained by probes used in the same PCR stages. The sequence analysis of the syncytin-1 and syncytin-2 genes were performed, and read by the usage of the FinchTV 1.4.0 program. RESULTS: Between the expression levels of syncytin-1 and syncytin-2 genes were statistically difference in the patients and controls. There was a difference (p < 0.0001) between trisomy 7 and other patient groups and controls, regarding to the expression of syncytin-1 gene. Numerous mutations in the syncytin-1 and syncytin-2 genes (on the expression sites) were detected, and the mutation rate was higher in the syncytin-1 gene compared to the syncytin-2 gene in the patient and in the control groups (p < 0.001). CONCLUSION: The results of the study indicate that the expression of the syncytin-2 genes could be altered in the presence of chromosomally abnormal trophoblastic tissues, and these could lead to the loss of pregnancy due to the insufficient syncytialization. In sum, the current research has value for the further studies covering the mechanisms of trophoblast cell fusion, and syncytiotrophoblast regeneration, and thus the pathophysiology of human placental development in the presence of genomic anomaly.