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1.
BMC Infect Dis ; 20(1): 724, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008310

RESUMO

BACKGROUND: Spinal neuroschistosomiasis (SN) is one of the most severe clinical presentations of schistosomiasis infection and an ectopic form of the disease caused by any species of Schistosoma. In Brazil, all cases of this clinical manifestation are related to Schistosoma mansoni, the only species present in the country. Although many cases have been reported in various endemic areas in Brazil, this is the first time in the literature that SN is described in two brothers. CASE PRESENTATION: Two cases of SN were accidentally diagnosed during an epidemiological survey in an urban area endemic for schistosomiasis transmission. Both patients complained of low back pain and muscle weakness in the lower limbs. Sphincter dysfunction and various degrees of paresthesia were also reported. The patients' disease was classified as hepato-intestinal stage schistosomiasis mansoni at the onset of the chronic form. A positive parasitological stool test for S. mansoni, clinical evidence of myeloradicular damage and exclusion of other causes of damage were the basic criteria for diagnosis. After treatment with praziquantel and corticosteroid, the patients presented an improvement in symptoms, although some complaints persisted. CONCLUSIONS: It is important to consider SN when patients come from areas endemic for transmission of schistosomiasis mansoni. Clinical physicians and neurologists should consider this diagnostic hypothesis, because recovery from neurological injuries is directly related to early treatment. As, described here in two brothers, a genetic predisposition may be related to neurological involvement. Primary care physicians should thus try to evaluate family members and close relatives in order to arrive at prompt schistosomiasis diagnosis in asymptomatic individuals and propose treatment in an attempt to avoid progression to SN.


Assuntos
Neuroesquistossomose/diagnóstico por imagem , Schistosoma mansoni , Esquistossomose mansoni/diagnóstico por imagem , Doenças da Coluna Vertebral/diagnóstico por imagem , Adulto , Animais , Brasil/epidemiologia , Progressão da Doença , Família , Humanos , Masculino , Debilidade Muscular , Neuroesquistossomose/fisiopatologia , Irmãos , Doenças da Coluna Vertebral/fisiopatologia
2.
Medicine (Baltimore) ; 99(41): e22497, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031286

RESUMO

RATIONALE: Paragangliomas (PGLs) are rare neuroendocrine tumors that are strongly influenced by genetics, and succinate dehydrogenase-deficient PGLs appear to constitute one of the most important categories. Interestingly, somatic PGLs only possess genomic alterations involving the SDHB and SDHD subunits, and no SDHA alterations have been described. Here, we are presenting the clinical and genetic analyses of 2 cases with the first somatic SDHA variant identified in PGLs. PATIENT CONCERNS: Here, we reported 2 family members with the diagnosis of PGL. Patient 1 is a 55-year-old woman with a functionally perigastric PGL that co-occurred with a gastric gastrointestinal stromal tumor (GIST), and patient 2 is a 43-year-old woman with a nonfunctionally pericardial PGL, who was the younger sister of the first patient. DIAGNOSES: Imaging surveys of the 2 cases depicted the presence of a perigastric and a pericardial mass, respectively. A diagnosis of paragangliomas was established by immunohistochemistry (IHC). INTERVENTIONS: Both patients underwent single-stage resection of the lesion after preoperative oral α-adrenoceptor therapy for 2 weeks. We later performed comprehensive genomic profiling on the tumor samples, including PGL and GIST from patient 1 and PGL from patient 2, and searched for novel actionable mutations, including in all succinate dehydrogenase subunits, as the IHC results were negative for SDHB. OUTCOMES: Both patients had an uneventful recovery after surgery and the sequencing showed a novel somatic variant in the SDHA gene on chromosome 5q11 (c.1945_1946delTT). Regular follow-up with biochemical testing and image studies showed no evidence of recurrence after a year for patient 1 and 6 years for patient 2. LESSONS: PGLs often lead to considerable diagnostic difficulty due to their multiple anatomical locations and variable symptoms, as presented by our cases. The comprehensive use of images and plasma/urine catecholamine measurement can aid the diagnosis of PGLs. In addition, our findings also demonstrate the usefulness and importance of genetic analysis of SDHA mutations in patients exhibiting SDHB IHC-negative PGL. Additional studies utilizing comprehensive genomic profiling are needed to identify the group of PGLs harboring this SDHA genomic alteration.


Assuntos
Complexo II de Transporte de Elétrons/genética , Tumores do Estroma Gastrointestinal/genética , Neoplasias Primárias Múltiplas/genética , Paraganglioma Extrassuprarrenal/genética , Neoplasias Gástricas/genética , Adulto , Feminino , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/patologia , Testes Genéticos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Mutação , Paraganglioma Extrassuprarrenal/diagnóstico , Paraganglioma Extrassuprarrenal/patologia , Irmãos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia
3.
Int Heart J ; 61(5): 1049-1055, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32921676

RESUMO

While a KCND3 V392I mutation uniquely displays a mixed electrophysiological phenotype of Kv4.3, only limited clinical information on the mutation carriers is available. We report two teenage siblings exhibiting both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral phenotypes (epilepsy and intellectual disability), in whom we identified the KCND3 V392I mutation. We propose a link between the KCND3 mutation with a mixed electrophysiological phenotype and cardiocerebral phenotypes, which may be defined as a novel cardiocerebral channelopathy.


Assuntos
Fibrilação Atrial/genética , Canalopatias/genética , Epilepsias Parciais/genética , Deficiência Intelectual/genética , Canais de Potássio Shal/genética , Adolescente , Morte Súbita Cardíaca , Eletrocardiografia , Eletroencefalografia , Feminino , Humanos , Pessoa de Meia-Idade , Mães , Mutação , Linhagem , Irmãos , Síncope/genética , Adulto Jovem
4.
Prax Kinderpsychol Kinderpsychiatr ; 69(6): 524-540, 2020 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-32988302

RESUMO

"If One Feels Better Like That …". Adolescent Sibling Relationship in the Context of Transgender Development A transgender development in youth can influence the relationship of concerned youth and their siblings. While in most surveys, the focus lies on transgender adolescents, both sides shall be interviewed here to capture the situation of siblings and to relate the results. For this purpose, guide interviews with ten transgender adolescents and twelve of their siblings were analysed in accordance to Grounded Theory. In most cases, participants were satisfied with the sibling relationship. After the coming-out of the transgender adolescent they showed both positive and negative reactions that, however, changed to respect and acceptance by time without exception. Doubt, compassion and grief were short lived and often replaced by joy for the transgender adolescent. Transgender youth were mostly satisfied with the reaction of their sibling though the amount of support varied. The time of coming-out and transition often led to an improvement in sibling relationship, more closeness and family cohesion. In general, siblings seem to be immediately concerned by transgenderism in adolescence. In clinical practice, they should thus be included from the beginning. By taking into account their situation, negative developments can be prevented, and the sibling relationship become usable as a resource.


Assuntos
Relações entre Irmãos , Irmãos/psicologia , Pessoas Transgênero/psicologia , Adolescente , Pesar , Humanos , Inquéritos e Questionários
5.
Zhonghua Xue Ye Xue Za Zhi ; 41(8): 624-629, 2020 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-32942814

RESUMO

Objective: To analyze the clinical characteristics and outcomes of non-aspergillus molds infection (NAMI) patients who underwent allogeneic stem cell transplantation. Methods: Total 24 patients diagnosed as proven or probable non-aspergillus molds infection after allo-HSCT at the Peking University Institute of Hematology from January 2010 to December 2016 were retrospectively reviewed. Results: Among the 24 non-aspergillus molds infection patients, 22 (91.6%) underwent haploidentical stem cell transplantation, while 1 (4.2%) underwent matched-sibling donor transplantation, and 1 (4.2%) underwent HLA-matched unrelated donor transplantation. Ten (41.7%) patients were diagnosed as proven NAMI, and 14 (58.3%) were probable NAMI. The median time to NAMI diagnosis was 188 (2-856) d after transplantation. Five (20.8%) patients had Mucorales infection, 14 (58.3%) Rhizopus infection, 3 (12.5%) had Absidia orchidis infection, and 2 (8.3%) had Scedosporium apiospermum infection. The response rate at was 38.9% (7/18) in 18 patients who adjusted antifungal therapy based on the etiology. After a median 229 (2-2280) days follow-up after diagnosis, the 2-year overall survival was (24.0±14.5) %. Conclusion: The major pathogen of NAMI after allo-HSCT was Rhizopus, and the mortality of NAMI after allo-HSCT was very high due to lack of early effective therapy.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções , Micoses/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Irmãos , Transplante Homólogo
6.
Plast Reconstr Surg ; 146(2): 355-365, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32740588

RESUMO

BACKGROUND: Craniosynostosis is one of the most common craniofacial malformations demanding surgical treatment in infancy. Data on overall psychiatric morbidity among children with nonsyndromic craniosynostosis remain limited. This study investigated the risk of psychiatric disorders in nonsyndromic craniosynostosis. METHODS: The authors reviewed a register-based cohort of all individuals born with nonsyndromic craniosynostosis in Sweden between 1973 to 1986 and 1997 to 2012 (n = 1238). The nonsyndromic craniosynostosis cohort was compared with a matched community cohort (n = 12,380) and with unaffected full siblings (n = 1485). The authors investigated the risk of psychiatric disorders, suicide attempts, and suicides by using Cox regression adjusted for perinatal and somatic factors, season and birth year, sex, parental socioeconomic factors, and parental psychiatric disorders. RESULTS: Children with nonsyndromic craniosynostosis had a higher risk of any psychiatric disorder (adjusted Cox-derived hazard ratio, 1.70; 95 percent CI, 1.43 to 2.02), including intellectual disability (adjusted Cox-derived hazard ratio, 4.96; 95 percent CI, 3.20 to 7.70), language disorders (adjusted Cox-derived hazard ratio, 2.36; 95 percent CI, 1.57 to 3.54), neurodevelopmental disorders (adjusted Cox-derived hazard ratio, 1.30; 95 percent CI, 1.01 to 1.69), and other psychiatric disorders (adjusted Cox-derived hazard ratio, 1.43; 95 percent CI, 1.11 to 1.85). Full siblings with nonsyndromic craniosynostosis were more likely, in the crude analyses, to be diagnosed with any psychiatric disorder, including intellectual disability, language disorders, and neurodevelopmental disorders compared with nonaffected siblings. The higher risk for any psychiatric disorder and intellectual disability remained after adjusting for confounders. CONCLUSIONS: Children with nonsyndromic craniosynostosis demonstrated higher risks of any psychiatric disorder compared with children without nonsyndromic craniosynostosis. This risk cannot fully be explained by familial influences (i.e., genetic or environmental factors). CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Assuntos
Craniossinostoses/complicações , Transtornos Mentais/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Craniossinostoses/epidemiologia , Feminino , Humanos , Incidência , Masculino , Transtornos Mentais/etiologia , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Irmãos , Suécia/epidemiologia
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1283-1291, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798413

RESUMO

OBJECTIVE: To analyze the effect of clinical features, routine laboratory examination and related gene mutation on the OS of patients with myelodysplastic syndrome (MDS) after hematopoietic stem cell transplantation (HSCT). METHODS: 121 patients diagnosed as MDS and underwent hematopoietic stem cell transplantation in the First Affiliated Hospital of Soochow University from October 2013 to August 2018 were selected. Basic information of the patients was collected, and blood cells, bone marrow blasts at initial diagnosis, chromosomal karyotypes and gene mutations of the patients were detected.The effect of different factors on overall survival (OS) was analyzed by statistical method. RESULTS: Kaplan-Meier univariate analysis shows that OS was significanly different among different age groups. The 3-year OS rate of patients aged 0-29 years was (83.3±7.7) %, the 3-year OS rate in patients aged 30-49 years was (58.1±7.7 %), and the 3-year OS rate of patients aged 50-69 years was (31.0±22.6) %, which was statistically different (P<0.05) between different groups. There were also significant differences in OS among patients with different transplantation types. 3-year OS rate: HLA-matched sibling HSCT>unrelated HLA-matched HSCT>haploidentical HSCT>micro HSCT. The OS rate of patients with bone marrow blasts≥10% seems lower than blasts<10%, but there was no statistical difference.The 3-year OS rate of patients with chromosomal karyotype complex abnormality was (47.7±11.5) %, and that of patients without complex abnormality was (80±4.2) % which was statistical difference (P<0.05). Patients with DNMT3A, NRAS, TP53 and GATA2 mutations had shorter OS time compared with patients without mutation of these genes, which shows statistically significant (P<0.05). COX multivariate analysis showed that age, chromosome karyotype, DNMT3A, TET2, GATA2 and NRAS were the independent factors influencing OS of patients after HSCT, with statistically significant difference. CONCLUSION: age of patients, donor selection of HSCT, chromosome karyotype, DNMT3A, NRAS, TP53, GATA2 and TET2 gene mutations are all independent factors affecting the OS of patients after HSCT. Therefore, the assessment of the OS of MDS patients with transplantation requires comprehensive consideration.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Adulto Jovem
8.
Pediatrics ; 146(3)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32817440

RESUMO

OBJECTIVES: To assess the relation between exposure to maternal depression before age 5 and 5 domains of developmental vulnerability at school entry, overall, and by age at exposure. METHODS: This cohort study included all children born in Manitoba, Canada, who completed the Early Development Instrument between 2005 and 2016 (N = 52 103). Maternal depression was defined by using physician visits, hospitalizations, and pharmaceutical data; developmental vulnerability was assessed by using the Early Development Instrument. Relative risk of developmental vulnerability was assessed by using log-binomial regression models adjusted for characteristics at birth. RESULTS: Children exposed to maternal depression before age 5 had a 17% higher risk of having at least 1 developmental vulnerability at school entry than did children not exposed to maternal depression before age 5. Exposure to maternal depression was most strongly associated with difficulties in social competence (adjusted relative risk [aRR] = 1.28; 95% confidence interval [CI]: 1.20-1.38), physical health and well-being (aRR = 1.28; 95% CI: 1.20-1.36), and emotional maturity (aRR = 1.27; 95% CI: 1.18-1.37). For most developmental domains, exposure to maternal depression before age 1 and between ages 4 and 5 had the strongest association with developmental vulnerability. CONCLUSIONS: Our finding that children exposed to maternal depression are at higher risk for developmental vulnerability at school entry is consistent with previous findings. We extended this literature by documenting that the adverse effects of exposure to maternal depression are specific to particular developmental domains and that these effects vary depending on the age at which the child is exposed to maternal depression.


Assuntos
Depressão/complicações , Deficiências do Desenvolvimento/etiologia , Nível de Saúde , Mães/psicologia , Habilidades Sociais , Pré-Escolar , Estudos de Coortes , Intervalos de Confiança , Depressão/diagnóstico , Depressão/epidemiologia , Depressão Pós-Parto/complicações , Feminino , Humanos , Lactente , Manitoba/epidemiologia , Risco , Irmãos/psicologia , Fatores Socioeconômicos , Adulto Jovem
9.
BMJ ; 370: m2533, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32816755

RESUMO

OBJECTIVES: To examine the long term mortality associated with preterm delivery in a large population based cohort of women, and to assess for potential confounding by shared familial factors. DESIGN: National cohort study. SETTING: Sweden. PARTICIPANTS: All 2 189 477 women with a singleton delivery in 1973-2015. MAIN OUTCOME MEASURES: All cause and cause specific mortality up to 2016, identified from nationwide death records. Cox regression was used to calculate hazard ratios while adjusting for confounders, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and environmental) factors. RESULTS: In 50.7 million person years of follow-up, 76 535 (3.5%) women died (median age at death was 57.6). In the 10 years after delivery, the adjusted hazard ratio for all cause mortality associated with preterm delivery (<37 weeks) was 1.73 (95% confidence interval 1.61 to 1.87), and when further stratified was 2.20 (1.63 to 2.96) for extremely preterm delivery (22-27 weeks), 2.28 (2.01 to 2.58) for very preterm delivery (28-33 weeks), 1.52 (1.39 to 1.67) for late preterm delivery (34-36 weeks), and 1.19 (1.12 to 1.27) for early term delivery (37-38 weeks) compared with full term delivery (39-41 weeks). These risks declined but remained significantly raised after longer follow-up times: for preterm versusfull term births, 10-19 years after delivery, the adjusted hazard ratio was 1.45 (95% confidence interval 1.37 to 1.53); 20-44 years after delivery, the adjusted hazard ratio was 1.37 (1.33 to 1.41). These findings did not seem to be attributable to shared genetic or environmental factors within families. Several causes were identified, including cardiovascular and respiratory disorders, diabetes, and cancer. CONCLUSIONS: In this large national cohort of women, the findings suggested that preterm and early term delivery were independent risk factors for premature mortality from several major causes. These associations declined over time but remained raised up to 40 years later.


Assuntos
Causas de Morte , Mortalidade/tendências , Mães/estatística & dados numéricos , Nascimento Prematuro/epidemiologia , Irmãos , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gravidez , Prevalência , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia
10.
Arch. argent. pediatr ; 118(4): 252-: I-257, I, agosto 2020. tab, ilus
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1118488

RESUMO

Introducción. La calidad de vida relacionada con la salud (CVRS) es una medida de resultado de salud. Evalúa el impacto subjetivo y global de las enfermedades en la vida cotidiana. Brinda información multidimensional sobre el bienestar físico, relación familiar y sus pares. Los estudios de CVRS de hermanos son limitados.Objetivo. Comparar CVRS de los hermanos de pacientes pediátricos con patologías reumáticas crónicas, trasplante renal o hepático con la de niños sanos con hermanos sin enfermedades crónicas.Resultados. Se compararon hermanos de niños con trasplante renal (n: 65), trasplante hepático (n: 35) y patologías reumáticas crónicas (n: 36) con el grupo control de niños sanos (n: 51). El grupo total de hermanos tuvieron puntuación más baja, estadísticamente significativa, en las dimensiones bienestar físico, amigos-apoyo social y recursos económicos. Los hermanos de trasplante renal tuvieron baja puntuación en las dimensiones de bienestar físico (p < 0,02; tamaño del efecto ­TE­: 0,66) y recursos económicos (p < 0,01; TE: 0,66). Los hermanos de trasplante hepático percibieron menor bienestar físico (p = 0,04), tenían menos amigos y apoyo social (p < 0,01), dificultades en el entorno escolar (p < 0,02) y recursos económicos (p < 0,01). Los hermanos de patologías reumáticas crónicas tuvieron menor bienestar físico (p < 0,05; TE: 0,44) y apoyo social-amigos (p < 0,01; TE: 0,58).Conclusión. La CVRS de niños/as sanos de hermanos con patologías crónicas es menor en bienestar físico, amigos-apoyo social y recursos económicos comparada con el grupo de niños sanos.


Introduction. Health-related quality of life (HRQoL) is a measure of health outcomes. It assesses the subjective and overall impact of diseases on daily life. It also provides multidimensional data about physical well-being, family and peers relations. HRQoL studies on siblings are limited.Objective. To compare HRQoL among siblings of pediatric patients with chronic rheumatic diseases, kidney or liver transplant and healthy children whose siblings had no chronic conditions.Results. The siblings of children with kidney transplant (n: 65), liver transplant (n: 35), and chronic rheumatic diseases (n: 36) were compared to the healthy children group (n: 51). The total siblings group had a lower, statistically significant score in the physical well-being, social support and peers, and financial resources dimensions. The siblings of kidney transplant patients had a low score in the physical well-being (p < 0.02; effect size [ES]: 0.66) and financial resources (p < 0.01; ES: 0.66) dimensions. The siblings of liver transplant patients perceived a lower physical well-being (p = 0.04), less social support and peers(p < 0.01), and difficulties in relation to school environment (p < 0.02) and financial resources (p < 0.01). The siblings of those with chronic rheumatic diseases had a lower score in the physical well-being (p < 0.05; ES: 0.44) and social support and peers (p < 0.01; ES: 0.58) dimensions.Conclusion. HRQoL among healthy children whose siblings have a chronic disease was lower in the physical well-being, social support and peers, and financial resources dimensions compared to the healthy children group.


Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Qualidade de Vida , Doença Crônica , Pacientes , Apoio Social , Estudos de Casos e Controles , Estudos Transversais , Irmãos , Relações Familiares
12.
PLoS One ; 15(6): e0234987, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603353

RESUMO

We investigate the link between birth order and the career outcome of becoming Chief Executive Officer (CEO) of a company. CEOs are more likely to be the first-born, i.e., oldest, child of their family relative to what one would expect if birth order did not matter for career outcomes. Both male and female CEOs are more likely to be first-born. However, the first-born advantage seems to largely reflect the absence of an older brother, but not of an older sister. These results are more pronounced for family firms, where traditionally the oldest child is appointed to run the family business, but also hold for non-family firms.


Assuntos
Ordem de Nascimento , Mobilidade Ocupacional , Comércio/organização & administração , Características da Família , Adulto , Fatores Etários , Comércio/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Irmãos , Inquéritos e Questionários/estatística & dados numéricos , Estados Unidos
13.
Medicine (Baltimore) ; 99(27): e20806, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629665

RESUMO

RATIONALE: DICER1 syndrome is an autosomal-dominant tumor predisposition syndrome associated with numerous cancerous and noncancerous conditions. The most common sex cord-stromal tumor associated with DICER1 syndrome is Sertoli-Leydig cell tumor of the ovary (SLCT), which is extremely unusual and accounts for < 0.5% of all ovarian neoplasms. SLCT predominantly affects adolescents and young female adults. To date, there are only a few case reports of ovarian SLCT with underlying germline DICER1 mutations. The diagnosis and treatment of this rare malignancy remains challenging in the clinic mainly due to its rarity and varied presentation. PATIENT CONCERNS: A 21-year-old Chinese girl (proband) was admitted in hospital for experiencing a lower abdominal pain and irregular vaginal bleeding for half a year. She was initially diagnosed with abdominal cavity mass prior to surgical operation. The other 20-year-old patient is the younger sister of the proband, who was diagnosed with ovarian cysts and had irregular menstruation and amenorrhea for 4 months. The elder sister underwent an uncomplicated bilateral ovarian tumor resection. Given a high degree of malignancy, comprehensive staged fertility-preserving surgery, including left adnexectomy, omentectomy, pelvic, and para-aortic lymphadenectomy, was performed. Since the other patient requested to maintain her fertility, tumor resection was only conducted in the right ovary. DIAGNOSES: The elder sister was diagnosed as poorly differentiated SLCT accompanied with heterologous stage IC rhabdomyosarcoma (RMS) based on its typical pathology features and molecular characteristics from immunohistochemistry (IHC) staining. The younger sister was diagnosed as poorly differentiated SLCT. Targeted next-generation sequencing (NGS) detected DICER1 mutation in the plasma samples and postoperative tumor tissues of both patients. INTERVENTIONS: Both patients underwent surgical tumor resection, followed by combination chemotherapy with bleomycin, etoposide, and cisplatin for 4 cycles. OUTCOMES: Patients received the above clinical interventions but eventually died from disease recurrence. The elder sister died from disease relapse after one and a half years postsurgery. The younger sister had a relapse of the disease 1 year later, but she refused the comprehensive staged surgery and died from disease relapse quickly. LESSONS: Ovarian SLCT patients with DICER1 mutations and a family history have a high degree of malignancy and are associated with a poor prognosis. With ongoing research efforts on DICER1 mutations, genetic screening and counselling on a regular basis is recommended for predicting potential future cancer risk of individuals with DICER1 syndrome family history.


Assuntos
RNA Helicases DEAD-box/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ribonuclease III/genética , Tumor de Células de Sertoli-Leydig/genética , Tumor de Células de Sertoli-Leydig/patologia , Feminino , Humanos , Neoplasias Ovarianas/terapia , Tumor de Células de Sertoli-Leydig/terapia , Irmãos , Adulto Jovem
14.
Isr Med Assoc J ; 7(22): 354-359, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692496

RESUMO

BACKGROUND: While the ratio of male to female births (sex-ratio at birth [SRB]) in humans is remarkably stable on the population level, there are many families with multiple same-sex offspring. OBJECTIVES: To identify a putative sub-population with skewed SRB and explore potential factors affecting the SRB. METHODS: A retrospective cohort study including 66,054 families with up to nine same-sex offspring evaluated between 2003 and 2015 at Hadassah-Hebrew University Medical Center. Outcome measures were observed prevalence and SRB of families with up to nine same-sex offspring in a single family. Analyses included the effect of parity, month and year of delivery, inter-delivery interval, and presence of a sequence of previous same-sex offspring on the SRB. RESULTS: The study comprised 193,411 live-born babies with SRB of 1.057 in favor of males. The proportion of SRB in families with up to nine same-sex offspring did not differ from the calculated presumed proportion. Furthermore, none of the tested factors (parity, month and year of delivery, inter-delivery interval, and the sequence of previous same-sex offspring) were significantly associated with SRB. CONCLUSIONS: SRB was not associated with any of the tested demographic characteristics. We could not identify a skew in SRB even in families with up to nine consecutive same sex offspring. This finding suggests that in the majority of the population the chance of a male or female fetus in each pregnancy remains similar in every pregnancy, regardless of any of the tested variables.


Assuntos
Distribuição por Sexo , Razão de Masculinidade , Irmãos , Estudos de Coortes , Feminino , Humanos , Israel , Masculino , Paridade , Gravidez , Estudos Retrospectivos
15.
Proc Natl Acad Sci U S A ; 117(30): 17695-17701, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32651279

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has led to a large increase in mortality in the United States and around the world, leaving many grieving the sudden loss of family members. We created an indicator-the COVID-19 bereavement multiplier-that estimates the average number of individuals who will experience the death of a close relative (defined as a grandparent, parent, sibling, spouse, or child) for each COVID-19 death. Using demographic microsimulation-based estimates of kinship networks in the United States, the clear age gradient in COVID-19 mortality seen across contexts, and several hypothetical infection prevalence scenarios, we estimate COVID-19 bereavement multipliers for White and Black individuals in the United States. Our analysis shows that for every COVID-19 death, approximately nine surviving Americans will lose a grandparent, parent, sibling, spouse, or child. These estimates imply, for example, that if 190,000 Americans die from COVID-19, as some models project, then ∼1.7 million will experience the death of a close relative. We demonstrate that our estimates of the bereavement multiplier are stable across epidemiological realities, including infection scenarios, total number of deaths, and the distribution of deaths, which means researchers can estimate the bereavement burden over the course of the epidemic in lockstep with rising death tolls. In addition, we provide estimates of bereavement multipliers by age group, types of kin loss, and race to illuminate prospective disparities. The bereavement multiplier is a useful indicator for tracking COVID-19's multiplicative impact as it reverberates across American families and can be tailored to other causes of death.


Assuntos
Luto , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/mortalidade , Grupos Étnicos/estatística & dados numéricos , Modelos Estatísticos , Pneumonia Viral/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Família , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Estudos Prospectivos , Irmãos , Cônjuges , Taxa de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
17.
DNA Cell Biol ; 39(10): 1754-1759, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32716646

RESUMO

Polydactyly frequently exhibits autosomal dominant inheritance, which is characterized by supernumerary fingers or toes. The growth of the limb was controlled by three signaling pathways in three-dimensional axis. Sonic Hedgehog signaling, which controls the anterior to posterior (radial to ulnar) orientation has been suspected to be a main cause for polydactyly. To determine the pathogenesis of the patients with polydactyly, we recruited a polydactyly family with two patients. Taking advantage of next-generation sequencing technology, we applied whole-exome sequencing and Sanger sequencing to the proband and her daughter. The analysis of the whole-exome sequencing showed a heterozygous missense mutation c.3617G>A (p.R1206H) in the PTCH1 gene. The results of Sanger sequencing also verified this mutation. Our research discovered a candidate gene of polydactyly-PTCH1. We are the first to point out the relationship between polydactyly and PTCH1 mutation in human. As the PTCH1 gene mutations have been identified in nevoid basal cell nevus syndrome (NBCCS), and polydactyly is one phenotype of NBCCS, it may provide a new clue to the study of the genotype-phenotype correlations between the PTCH1 gene mutations and NBCCS.


Assuntos
Mutação de Sentido Incorreto , Receptor Patched-1/genética , Polidactilia/genética , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Polidactilia/patologia , Irmãos
18.
Ann Biol Clin (Paris) ; 78(4): 425-432, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32618564

RESUMO

Wilson disease is a rare inherited disorder of copper metabolism that affects liver and brain due to copper tissue accumulation. The mechanism involved is based on mutations of the ATP7B gene. Children have predominant hepatic manifestations while adult are more often diagnosed by neurological and psychiatric symptoms. However, others features are tubulopathy, articular disorders and hemolytic anemia. We report the diagnostic of Wilson disease in a 14 years old girl and her sibling after investigation of hemolytic anemia, hepatic insufficiency, and hypophosphatemia.


Assuntos
Anemia Hemolítica/diagnóstico , Degeneração Hepatolenticular/diagnóstico , Doença Aguda , Adolescente , Anemia Hemolítica/complicações , Criança , Pré-Escolar , ATPases Transportadoras de Cobre/genética , Diagnóstico Diferencial , Família , Feminino , Hemólise/fisiologia , Insuficiência Hepática/complicações , Insuficiência Hepática/diagnóstico , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/genética , Humanos , Hipofosfatemia/complicações , Hipofosfatemia/diagnóstico , Masculino , Irmãos
19.
PLoS One ; 15(7): e0236261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687510

RESUMO

Dietary and physical activity behaviors formed early in life can increase risk for childhood obesity and have continued negative consequences for lifelong health. Previous research has highlighted the importance of both genetic and environmental (e.g., cultural environment or parental lifestyle) contributions to obesity risk, although these studies typically involve genetically-related individuals residing in the same household, where genetic similarity and rearing environment are inextricably linked. Here we utilize a sibling-adoption design to independently estimate genetic and environmental contributions to obesity risk in childhood and describe how these influences might vary as children age. As part of a prospective adoption study, the current investigation used data from biological siblings reared either apart or together, and nonbiological siblings reared together to estimate the contributions of genetics and environment to body mass indices (BMI) in a large cohort of children (N = 711). We used a variance partitioning model to allocate variation in BMI to that which is due to shared genetics, common environment, or unique environment in this cohort during middle childhood and adolescence. We found 63% of the total variance in BMI could be attributed to heritable factors in middle childhood sibling pairs (age 5-11.99; 95% CI [0.41,0.85]). Additionally, we observed that common environment explained 31% of variation in BMI in this group (95% CI [0.11,0.5]), with unique environment and error explaining the remaining variance. We failed to detect an influence of genetics or common environment in older sibling pairs (12-18) or pairs spanning childhood and adolescence (large sibling age difference), but home type (adoptive versus birth) was an important predictor of BMI in adolescence. The presence of strong common environment effects during childhood suggests that early interventions at the family level in middle childhood could be effective in mitigating obesity risk in later childhood and adolescence.


Assuntos
Adoção , Índice de Massa Corporal , Interação Gene-Ambiente , Obesidade Pediátrica/epidemiologia , Irmãos , Adolescente , Criança , Desenvolvimento Infantil/fisiologia , Educação Infantil , Pré-Escolar , Feminino , Humanos , Masculino , Obesidade Pediátrica/genética , Obesidade Pediátrica/fisiopatologia , Obesidade Pediátrica/prevenção & controle , Estudos Prospectivos
20.
BMC Neurol ; 20(1): 258, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600288

RESUMO

BACKGROUND: Leukodystrophies are familial heterogeneous disorders primarily affecting the white matter, which are defined as hypomyelinating or demyelinating based on disease severity as assessed at MRI. Recently, a group of clinically overlapping hypomyelinating leukodystrophies (HL) has been associated with mutations in RNA polymerase III enzymes (Pol III) subunits. CASE PRESENTATION: In this manuscript, we describe two Italian siblings carrying a novel POLR3A genotype. MRI imaging, genetic analysis, and clinical data led to diagnosing HL type 7. The female sibling, at the age of 34, is tetra-paretic and suffers from severe cognitive regression. She had a disease onset at the age of 19, characterized by slow and progressive cognitive impairment associated with gait disturbances and amenorrhea. The male sibling was diagnosed during an MRI carried out for cephalalgia at the age of 41. After 5 years, he developed mild cognitive impairment, dystonia with 4-limb hypotonia, and moderate dysmetria with balance and gait impairment. CONCLUSIONS: The present study provides the first evidence of unusually late age of onset in HL, describing two siblings with a novel POLR3A genotype which showed the first symptoms at the age of 41 and 19, respectively. This provides a powerful insight into clinical heterogeneity and genotype-phenotype correlation in POLR3A related HL.


Assuntos
Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , RNA Polimerase III/genética , Adulto , Idade de Início , Encéfalo/patologia , Feminino , Genótipo , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Mutação , Irmãos , Substância Branca/patologia
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