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1.
Am J Med Genet A ; : e63816, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007708

RESUMO

RFX7 encodes a transcription factor that is ubiquitously expressed and important for neural development. Haploinsufficiency of RFX7 is associated with intellectual disability, developmental delay, and diverse malformations of brain structures. Currently, there are only 16 clinically described individuals who have variants in RFX7. A recognizable pattern of malformation associated with mutation in RFX7 has not yet been uncovered. Here we describe the phenotypic presentation of two additional individuals who have novel de novo variants in RFX7. One of the individuals we describe is from an under-represented Afro-Caribbean population.

2.
Rev Panam Salud Publica ; 46: e135, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060198

RESUMO

This study aims to assess coronavirus disease 2019 (COVID-19) surveillance methods, health resources, vaccination coverage and income stratification and quantify burdens of disease and death in children and adolescents in the Caribbean. The investigation was a descriptive, cross-sectional study that included 15 Caribbean countries/territories and utilized surveys and secondary data sources. Quarantine and isolation measures were robust and surveillance strategies were similar. Pediatric specialists were available across the region, but few had designated pediatric hospitals or high-dependency units. There were more cases in children on islands with larger populations. Compared to high-income countries/territories, upper and lower middle-income countries/territories had higher disease burdens, fewer doctors and nurses per 1 000 population, lower bed capacities, and lower vaccination coverage. Child and adolescent cases ranged from 0.60% to 16.9%, compared with a global case rate of 20.2% in 2021. By August 2021 there were 33 deaths among children from Haiti, Jamaica, Trinidad and Tobago, and Barbados. The respective case fatality rates for 0-9-year-olds and 10-19-year-olds were 2.80 and 0.70 in Haiti, 0.10 and 0.20 in Jamaica, and 0.00 and 0.14 in Trinidad, compared with 0.17 and 0.1 globally. Overall COVID-19 incidence and mortality in children were consistent with global estimates. Limited resources have been offset by availability of pediatricians across the region, and minimally direct effects on children. Prioritization of admission of specific at-risk groups, training of first responders and vaccination campaigns targeting pregnant women and vulnerable children and adolescents could benefit countries with low vaccine coverage rates and limited resources.


El presente estudio tiene como objetivo evaluar los métodos de vigilancia, los recursos de salud, y la cobertura de vacunación y la estratificación de los ingresos, así como cuantificar las cargas de enfermedad y muerte de la enfermedad por coronavirus del 2019 (COVID-19) en niños, niñas y adolescentes en el Caribe. La investigación consistió en un estudio descriptivo y transversal que incluyó a 15 países o territorios del Caribe y empleó encuestas y fuentes de datos secundarios. Las medidas de cuarentena y aislamiento fueron sólidas, igual que las estrategias de vigilancia. Había especialistas pediátricos disponibles en toda la región, pero pocos designados en hospitales pediátricos o unidades de alta dependencia. Hubo más casos en pacientes pediátricos en las islas más pobladas. En comparación con los países y territorios de ingresos altos, los de ingresos medianos altos y medianos bajos presentaron una mayor carga de morbilidad, menos personal médico y de enfermería por 1 000 habitantes, menor capacidad de camas y menor cobertura de vacunación. Los casos de niños, niñas y adolescentes oscilaron entre 0,60% y 16,9%, en comparación con una tasa general de casos de 20,2% en el 2021. En agosto del 2021, hubo 33 muertes de pacientes pediátricos de Haití, Jamaica, Trinidad y Tabago y Barbados. Las tasas de mortalidad de los grupos etarios de 0 a 9 años y de 10 a 19 años fueron respectivamente de 2,80 y 0,70 en Haití; 0,10 y 0,20 en Jamaica; y 0,00 y 0,14 en Trinidad; en comparación con 0,17 y 0,1 a nivel mundial. La incidencia general de COVID-19 y la mortalidad en la población infantil fueron coherentes con las estimaciones mundiales. Se compensaron los recursos limitados con la disponibilidad de pediatras en toda la región y efectos directos mínimos en los niños. Priorizar la admisión de grupos específicos de riesgo, la capacitación de los equipos de respuesta inicial y las campañas de vacunación dirigidas a mujeres embarazadas y niños, niñas y adolescentes vulnerables podría beneficiar a los países con recursos limitados y bajas tasas de cobertura de vacunación.


Este estudo visa a avaliar os métodos de vigilância, recursos de saúde, cobertura vacinal e estratificação de renda relacionados à doença do coronavírus de 2019 (COVID-19) e quantificar a carga de morbimortalidade a ela atribuível em crianças e adolescentes no Caribe. Foi realizado um estudo descritivo e transversal que incluiu 15 países e territórios caribenhos e utilizaram-se levantamentos e fontes de dados secundárias. As medidas de quarentena e isolamento foram robustas, e as estratégias de vigilância foram semelhantes. Houve disponibilidade de especialistas pediátricos em toda a região, mas poucos países/territórios tinham hospitais pediátricos ou unidades semi-intensivas especificamente designados. Ocorreram mais casos em crianças nas ilhas com populações maiores. Em comparação com os países/territórios de alta renda, aqueles de renda média-alta e média-baixa apresentaram uma maior carga de morbidade, menos médicos e enfermeiros por 1 000 habitantes, menor capacidade de leitos e menor cobertura vacinal. De 0,60% a 16,9% dos casos ocorreram em crianças e adolescentes, contra uma média mundial de 20,2% em 2021. Até agosto de 2021, haviam ocorrido 33 óbitos de crianças em Barbados, Haiti, Jamaica e Trinidad e Tobago. Os respectivos índices de letalidade nas faixas etárias de 0-9 anos e de 10-19 anos foram 2,80 e 0,70 no Haiti, 0,10 e 0,20 na Jamaica e 0,00 e 0,14 em Trinidad, em comparação com 0,17 e 0,1 no âmbito mundial. Em geral, a incidência e a mortalidade por COVID-19 em crianças foram condizentes com as estimativas mundiais. Os recursos limitados foram compensados pela disponibilidade de pediatras em toda a região e pelos pouquíssimos efeitos diretos sobre as crianças. Priorização de grupos de risco específicos para internação, treinamento de socorristas e campanhas de vacinação dirigidas a gestantes e a crianças e adolescentes vulneráveis poderiam beneficiar países com baixos índices de cobertura vacinal e recursos limitados.

3.
Am J Med Genet A ; 185(6): 1649-1665, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33783954

RESUMO

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype-phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype-phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.


Assuntos
Predisposição Genética para Doença , Transtornos do Crescimento/genética , Histona-Lisina N-Metiltransferase/genética , Hipertricose/congênito , Deficiência Intelectual/genética , Proteína de Leucina Linfoide-Mieloide/genética , População Negra/genética , Constipação Intestinal/epidemiologia , Constipação Intestinal/genética , Constipação Intestinal/patologia , Insuficiência de Crescimento/epidemiologia , Insuficiência de Crescimento/genética , Insuficiência de Crescimento/patologia , Estudos de Associação Genética , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/patologia , Humanos , Hipertricose/epidemiologia , Hipertricose/genética , Hipertricose/patologia , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/patologia , Mutação com Perda de Função/genética , Estudos Retrospectivos , População Branca/genética
4.
Am J Med Genet C Semin Med Genet ; 184(4): 965-969, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33258203

RESUMO

Most of the geographically isolated island nations in the Caribbean have small populations and low gross national product. As such, many lack important medical and community services. Difficulties are compounded when attempting to care for children with special needs and genetic disorders such as Down syndrome. International charitable organizations can help to provide much needed specialty medical care. Community associations can encourage local relationship building and education. Collaborative efforts with well-funded laboratories can help to deliver molecular characterization for individuals who have genetic disorders. With community and volunteer effort, a higher standard of care is obtainable in underserved communities.


Assuntos
Síndrome de Down , Região do Caribe , Criança , Síndrome de Down/terapia , Humanos , Índias Ocidentais
5.
Am J Med Genet C Semin Med Genet ; 184(4): 1030-1041, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33274544

RESUMO

We describe our experiences with organizing pro bono medical genetics and neurology outreach programs on several different resource-limited islands in the West Indies. Due to geographic isolation, small population sizes, and socioeconomic disparities, most Caribbean islands lack medical services for managing, diagnosing, and counseling individuals with genetic disorders. From 2015 to 2019, we organized 2-3 clinics per year on various islands in the Caribbean. We also organized a week-long clinic to provide evaluations for children suspected of having autism spectrum disorder. Consultations for over 100 different individuals with suspected genetic disorders were performed in clinics or during home visits following referral by locally registered physicians. When possible, follow-up visits were attempted. When available and appropriate, clinical samples were shipped to collaborating laboratories for molecular analysis. Laboratory tests included karyotyping, cytogenomic microarray analysis, exome sequencing, triplet repeat expansion testing, blood amino acid level determination, biochemical assaying, and metabolomic profiling. We believe that significant contributions to healthcare by genetics professionals can be made even if availability is limited. Visiting geneticists may help by providing continuing medical education seminars. Clinical teaching rounds help to inform local physicians regarding the management of genetic disorders with the aim of generating awareness of genetic conditions. Even when only periodically available, a visiting geneticist may benefit affected individuals, their families, their local physicians, and the community at large.


Assuntos
Transtorno do Espectro Autista , Médicos , Criança , Atenção à Saúde , Humanos , Encaminhamento e Consulta , Índias Ocidentais
6.
Am J Med Genet A ; 182(8): 1877-1880, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32618095

RESUMO

NALCN encodes a sodium ion leak channel expressed in the nervous system that conducts a persistent influx of sodium ions to facilitate action potential formation. Homozygous or compound heterozygous loss of function variants in NALCN cause infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1; OMIM 615419). Through exome and Sanger sequencing, we found two siblings of Afro-Caribbean ancestry who are homozygous for a known NALCN pathogenic variant, p.Arg735Ter, leading to failure to thrive, severe hypotonia, and dolichocephaly. The older sibling died suddenly without a known etiology after evaluation but before molecular diagnosis. An international collaboration originating from a resource limited Caribbean island facilitated molecular diagnosis. Due to its small population, geographical isolation, and low socioeconomic status, the island lacks many specialty medical services, including clinical genetics. Descriptions of genetic disorders affecting individuals of Afro-Caribbean ancestry are rarely reported in the medical literature. Diagnosis of IHPRF1 is important, as individuals with biallelic pathogenic NALCN variants are severely affected and potentially are at risk for cardiorespiratory arrest. Additionally, knowing the pathogenic variants allows the possibility of prenatal or preimplantation genetic diagnosis.


Assuntos
Predisposição Genética para Doença , Canais Iônicos/genética , Proteínas de Membrana/genética , Hipotonia Muscular/genética , Transtornos Psicomotores/genética , Região do Caribe , Exoma/genética , Feminino , Homozigoto , Humanos , Lactente , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Deficiência Intelectual/patologia , Masculino , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/patologia , Mutação de Sentido Incorreto/genética , Transtornos Psicomotores/diagnóstico , Transtornos Psicomotores/patologia , Irmãos
7.
Am J Med Genet A ; 176(2): 483-486, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29278455

RESUMO

It is a matter of course that in high-income countries, infants born with features suggestive of Down syndrome (DS) are offered genetic testing for confirmation of a clinical diagnosis. Benefits of a definitive diagnosis include an end to the diagnostic odyssey, informed prognosis, opportunities for caregiver support, inclusion to social support networks, and more meaningful genetic counseling. The healthcare experience for families of children born with DS in low- and middle-income nations is in stark contrast with such a level of care. Barriers to obtaining genetic diagnosis might include economic disparities, geographical isolation, and lack of access to health care professionals trained in genetic medicine. As part of a combined research and community outreach effort, we provided genetic testing for several patients with DS. These individuals and their families live on several resource-limited Caribbean islands and have either limited or virtually no access to medical genetics services. Within this group were three families with recurrent DS. Karyotype established that translocation events were not involved in the DS in any of these families. This information enabled genetic counseling to help family members understand their recurrent DS. A definitive diagnosis of DS is beneficial to families in resource-limited communities and may help to provide such families with genetic counseling, reassurance, and peace of mind.


Assuntos
Síndrome de Down/diagnóstico , Síndrome de Down/genética , Aconselhamento Genético , Testes Genéticos , Criança , Síndrome de Down/epidemiologia , Síndrome de Down/fisiopatologia , Família , Feminino , Serviços em Genética , Humanos , Lactente , Masculino , Linhagem , Apoio Social
8.
Epilepsy Behav ; 51: 267-72, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26312988

RESUMO

Very little has been reported about the health resources available for patients with epilepsy in the five English-speaking southern Caribbean countries of Trinidad and Tobago, Barbados, Grenada, Saint Vincent and the Grenadines, and Saint Lucia. There is no comprehensive resource describing their health systems, access to specialty care, antiepileptic drug (AED) use, and availability of brain imaging and EEG. The purpose of this study was to profile epilepsy care in these countries as an initial step toward improving the standard of care and identifying gaps in care to guide future policy changes. In each southern Caribbean country, we conducted study visits and interviewed health-care providers, government health ministers, pharmacy directors, hospital medical directors, pharmacists, clinic staff, radiologists, and radiology and EEG technicians. Health-care providers completed extensive epilepsy care surveys. The five countries all have integrated government health systems with clinics and hospitals that provide free or heavily subsidized care and AEDs for patients with epilepsy. Only Trinidad and Tobago and Barbados, however, have neurology specialists. The three smaller countries lack government imaging and EEG facilities. Trinidad had up to one-year waits for public MRI/EEG. Government formularies in Grenada, Saint Vincent and the Grenadines, and Saint Lucia are limited to first-generation AEDs. One or more second-line agents are formulary in Trinidad and Barbados. Nonformulary drugs may be obtained for individual patients in Barbados. Grenada, Saint Lucia, and Saint Vincent and the Grenadines participate in an Organization of Eastern Caribbean States formulary purchasing system, which added levetiracetam following the survey. Newer generic AED formulations with the lowest risks for pregnancy malformation were not in use. In conclusion, patients with epilepsy in the southern Caribbean have excellent access to government clinics and hospitals, but AED choices are limited. Local medical providers reported that the major limitations in care were lack of specialty care, lack of imaging and EEG services, financial barriers to care, long wait times for care, and limited access to additional AEDs.


Assuntos
Atenção à Saúde/estatística & dados numéricos , Epilepsia/epidemiologia , Epilepsia/terapia , Anticonvulsivantes/provisão & distribuição , Barbados , Região do Caribe/epidemiologia , Países em Desenvolvimento , Uso de Medicamentos , Eletroencefalografia , Feminino , Formulários Farmacêuticos como Assunto , Pessoal de Saúde/estatística & dados numéricos , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Humanos , Masculino , Neurologia/estatística & dados numéricos , Gravidez , Santa Lúcia , São Vicente e Granadinas
9.
Mod Pathol ; 27(6): 800-7, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24201122

RESUMO

Subcutaneous panniculitis-like T-cell lymphoma is a rare subtype of cutaneous T-cell lymphoma. Virtually all cases are confined to the subcutaneous adipose tissue. In this report, we describe the first small series of subcutaneous panniculitis-like T-cell lymphoma (three patients) with bone marrow involvement. All patients presented with skin or soft tissue nodules, fever, and constitutional symptoms, and were diagnosed with subcutaneous panniculitis-like T-cell lymphoma based on the characteristic morphologic and immunophenotypic features of the subcutaneous lesions. Bone marrow core biopsies in these cases showed focal involvement by lymphoma with pathologic features similar to those seen in the diagnostic biopsies. Our observations suggest bone marrow involvement by subcutaneous panniculitis-like T-cell lymphoma does occur, and can be identified histologically and confirmed using standard immunohistochemistry. Our findings raise awareness of bone marrow involvement in this rare entity. However, the incidence and significance of bone marrow involvement in subcutaneous panniculitis-like T-cell lymphoma requires further evaluation.


Assuntos
Medula Óssea/patologia , Linfoma de Células T/patologia , Paniculite/patologia , Adulto , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto Jovem
10.
Mol Genet Genomic Med ; 11(1): e2064, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36148638

RESUMO

BACKGROUND: SYNJ1 encodes Synaptojanin-1, a dual-function poly-phosphoinositide phosphatase that is expressed in the brain to regulate neuronal synaptic vesicle dynamics. Biallelic SYNJ1 variants cause a spectrum of clinical manifestations, from early onset parkinsonism to developmental and epileptic encephalopathy. METHODS: Proband-only exome sequencing was used to identify a homozygous SYNJ1 pathogenic variant in an individual with epileptic encephalopathy. Sanger sequencing was used to confirm the variant. RESULTS: We present an Afro-Caribbean female who developed uncontrollable seizures shortly after birth, accompanied by developmental delay and severe generalized dystonia. She had homozygosity for a novel c.242-2A > G variant in SYNJ1 with both parents being heterozygous carriers. An older sister was reported to have had a similar presentation but was not examined. Both siblings died at an approximate age of 16 years. CONCLUSIONS: We report a novel pathogenic variant in SYNJ1 present in homozygosity leading to developmental and epileptic encephalopathy. Currently, there are only 4 reports describing 10 individuals with SYNJ1-related developmental and epileptic encephalopathy. This case expands the clinical knowledge and the allelic heterogeneity associated with SYNJ1 variants.


Assuntos
Epilepsia Generalizada , Humanos , Feminino , Adolescente , Homozigoto , Encéfalo , Convulsões , Região do Caribe
12.
Mol Genet Genomic Med ; 10(4): e1900, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35189041

RESUMO

BACKGROUND: Individuals with various sized terminal duplications of chromosome 5p or terminal deletions of chromosome 18q have been described. These aberrations may cause congenital malformations and intellectual disability of varying severity. METHODS: Via an international collaborative effort, we obtained a cytogenetic diagnosis for a 5-year-old boy of Afro-Caribbean ancestry who has global developmental delay, dysmorphology, hypotonia, feeding difficulties, bilateral club feet, and intellectual disability. RESULTS: Conventional G-banded karyotyping showed additional chromatin of unknown origin on the long arm of chromosome 18. SNP microarray confirmed the loss of ~6.4 Mb from chromosome 18q: arr[hg19] 18q22.3-q23(71,518,518-77,943,115)x1. The source of the additional chromatin was determined from the microarray to be ~32 Mb from the short arm of chromosome 5 (arr[hg19] 5p13.3-p15.33(51,045-32,062,984)x3). The unbalanced translocation was verified by fluorescent in situ hybridization (FISH). Both parents are healthy and have normal karyotypes suggesting that this abnormality arose de novo in the proband, although gonadal mosaicism in a parent cannot be excluded. CONCLUSION: The combination of clinical features in this individual is most likely due to the partial deletion of 18q and partial duplication of 5p, which to our knowledge has not been previously described.


Assuntos
Cromossomos Humanos Par 18 , Deficiência Intelectual , Cromatina , Humanos , Hibridização in Situ Fluorescente , Deficiência Intelectual/genética , Translocação Genética
13.
HGG Adv ; 3(3): 100102, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35469323

RESUMO

Loss-of-function variants in PHD Finger Protein 8 (PHF8) cause Siderius X-linked intellectual disability (ID) syndrome, hereafter called PHF8-XLID. PHF8 is a histone demethylase that is important for epigenetic regulation of gene expression. PHF8-XLID is an under-characterized disorder with only five previous reports describing different PHF8 predicted loss-of-function variants in eight individuals. Features of PHF8-XLID include ID and craniofacial dysmorphology. In this report we present 16 additional individuals with PHF8-XLID from 11 different families of diverse ancestry. We also present five individuals from four different families who have ID and a variant of unknown significance in PHF8 with no other explanatory variant in another gene. All affected individuals exhibited developmental delay and all but two had borderline to severe ID. Of the two who did not have ID, one had dyscalculia and the other had mild learning difficulties. Craniofacial findings such as hypertelorism, microcephaly, elongated face, ptosis, and mild facial asymmetry were found in some affected individuals. Orofacial clefting was seen in three individuals from our cohort, suggesting that this feature is less common than previously reported. Autism spectrum disorder and attention deficit hyperactivity disorder, which were not previously emphasized in PHF8-XLID, were frequently observed in affected individuals. This series expands the clinical phenotype of this rare ID syndrome caused by loss of PHF8 function.

14.
Mod Pathol ; 24(11): 1433-43, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21685909

RESUMO

Lymphoid-enhancer-binding factor 1 (LEF1), coupling with ß-catenin, functions as a key nuclear mediator of WNT/ß-catenin signaling, which regulates cell proliferation and survival. LEF1 has an important role in lymphopoiesis, and is normally expressed in T and pro-B cells but not mature B cells. However, gene expression profiling demonstrates overexpression of LEF1 in chronic lymphocytic leukemia, and knockdown of LEF1 decreases the survival of the leukemic cells. So far, the data on LEF1 expression in B-cell lymphomas are limited. This study represents the first attempt to assess LEF1 by immunohistochemistry in a large series (290 cases) of B-cell lymphomas. Strong nuclear staining of LEF1 was observed in virtually all neoplastic cells in 92 of 92 (100%) chronic lymphocytic leukemia/small lymphocytic lymphomas including two CD5- cases, with strongest staining in cells with Richter's transformation. LEF1 also highlighted the morphologically inconspicuous small lymphocytic lymphoma component in three composite lymphomas. All 53 mantle cell lymphomas, 31 low-grade follicular lymphomas and 31 marginal zone lymphomas, including 3 CD5+ cases, were negative. In 12 grade 3 follicular lymphomas, LEF1 was positive in a small subset (5-15%) of cells. Diffuse large B-cell lymphoma, however, demonstrated significant variability in LEF1 expression with overall positivity in 27 of 71 (38%) cases. Our results demonstrate that nuclear overexpression of LEF1 is highly associated with chronic lymphocytic leukemia/small lymphocytic lymphoma, and may serve as a convenient marker for differential diagnosis of small B-cell lymphomas. The expression of ß-catenin, the coactivator of LEF1 in WNT signaling, was examined in 50 chronic lymphocytic leukemia/small lymphocytic lymphomas, of which 44 (88%) showed negative nuclear staining. The findings of universal nuclear overexpression of LEF1 but lack of nuclear ß-catenin in the majority of chronic lymphocytic leukemia/small lymphocytic lymphoma suggest that the pro-survival function of LEF1 in this disease may be independent of WNT/ß-catenin signaling.


Assuntos
Biomarcadores Tumorais/análise , Núcleo Celular/química , Leucemia Linfocítica Crônica de Células B/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide/análise , Linfoma de Células B/química , Chicago , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Leucemia Linfocítica Crônica de Células B/patologia , Linfoma de Células B/patologia , Linfoma de Zona Marginal Tipo Células B/química , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Folicular/química , Linfoma Folicular/patologia , Linfoma Difuso de Grandes Células B/química , Linfoma Difuso de Grandes Células B/patologia , Linfoma de Célula do Manto/química , Linfoma de Célula do Manto/patologia , Valor Preditivo dos Testes , Regulação para Cima , beta Catenina/análise
15.
Mol Genet Genomic Med ; 9(1): e1567, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332776

RESUMO

BACKGROUND: Grenada is a small, resource-limited Caribbean country with a high incidence of sickle cell disease (SCD). Since little is known about the challenges facing individuals living with SCD in the West Indies, we sought to assess barriers to healthcare and the impact of SCD on quality of life in Grenada. METHODS: Both adults aged 18+ (n = 19) and caregivers of children aged 2-17 (n = 26) completed validated survey measures regarding barriers to care and quality of life, along with a genetics knowledge questionnaire. Caregivers also completed a caregiver burden scale. Survey scores were calculated, and responses were analyzed for an association between demographic variables. RESULTS: The Barriers to Care Questionnaire, in which lower scores indicate more barriers, revealed that both adults (mean = 69.9) and children (mean = 75.5) with SCD experienced reduced access to care. The Adult Sickle Cell Quality of Life Measurement Information System indicated increased depression and loneliness in adults, with the lowest scores in the Emotional subscale. However, the Pediatric Quality of Life Inventory answered by caregivers of children with SCD showed the lowest scores in the Physical Functioning subscale. Further analysis using the Caregiver Burden Scale-Zarit Burden Interview revealed that 53.8% of caregivers of children with SCD indicated "little to no burden," which may reflect a difference in cultural expectations of a caregiver between high-income countries and Grenada. Finally, ~80% of respondents knew that SCD was a genetic condition; however, 61%-84% could not correctly indicate recurrence risks, demonstrating a need for additional education. CONCLUSION: These data provide new insights regarding the experience of living with SCD in Grenada and support the need for further investigations into specific barriers to healthcare delivery, which could also improve education and well-being for those affected by SCD in Grenada and in the broader Caribbean community.


Assuntos
Anemia Falciforme/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde , Qualidade de Vida , Adolescente , Adulto , Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Cuidadores/psicologia , Criança , Pré-Escolar , Granada , Humanos , Satisfação do Paciente
16.
Oncology (Williston Park) ; 24(7): 574-87, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20669794

RESUMO

Anaplastic large cell lymphoma (ALCL) is a biologic and clinically heterogenous subtype of T-cell lymphoma. Clinically, ALCL may present as localized (primary) cutaneous disease or widespread systemic disease. These two forms of ALCL are distinct entities with different clinical and biologic features. Both types share similar histology, however, with cohesive sheets of large lymphoid cells expressing the Ki-1 (CD30) molecule. Primary cutaneous ALCL (C-ALCL) is part of the spectrum of CD30+ lymphoproliferative diseases of the skin including lymphomatoid papulosis. Using conservative measures, 5-year disease-free survival rates are > 90%. The systemic ALCL type is an aggressive lymphoma that may secondarily involve the skin, in addition to other extranodal sites. Further, systemic ALCL may be divided based on the expression of anaplastic lymphoma kinase (ALK) protein, which is activated most frequently through the nonrandom t(2;5) chromosome translocation, causing the fusion of the nucleophosmin (NPM) gene located at 5q35 to 2p23 encoding the receptor tyrosine kinase ALK. Systemic ALK+ ALCLs have improved prognosis compared with ALK-negative ALCL, although both subtypes warrant treatment with polychemotherapy. Allogeneic and, to a lesser extent, autologous stem cell transplantation play a role in relapsed disease, while the benefit of upfront transplant is not clearly defined. Treatment options for relapsed patients include agents such as pralatrexate (Folotyn) and vinblastine. In addition, a multitude of novel therapeutics are being studied, including anti-CD30 antibodies, histone deacetylase inhibitors, immunomodulatory drugs, proteasome inhibitors, and inhibitors of ALK and its downstream signaling pathways. Continued clinical trial involvement by oncologists and patients is imperative to improve the outcomes for this malignancy.


Assuntos
Linfoma Anaplásico de Células Grandes/patologia , Linfoma Anaplásico de Células Grandes/terapia , Linfoma Anaplásico Cutâneo Primário de Células Grandes/patologia , Linfoma Anaplásico Cutâneo Primário de Células Grandes/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Humanos , Imunofenotipagem , Antígeno Ki-1/fisiologia , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico Cutâneo Primário de Células Grandes/genética , Neoplasias Cutâneas/genética
17.
J Nurs Adm ; 40(4): 162-8, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20305461

RESUMO

Bedside nurses are well positioned to make changes that positively affect operations and practice. Using Transforming Care at the Bedside processes and methods, the authors describe the clinical nurse-led development, testing, and implementation of an electronic template and process for change-of-shift report. Outcomes included a reduction in time spent in change-of-shift reports, reduced end-of-shift overtime, and a more standardized process, with staff perceived improved information quality and satisfaction with the process.


Assuntos
Controle de Formulários e Registros/organização & administração , Relações Interprofissionais , Sistemas Computadorizados de Registros Médicos/organização & administração , Recursos Humanos de Enfermagem Hospitalar/organização & administração , Planejamento de Assistência ao Paciente/organização & administração , Sistemas Automatizados de Assistência Junto ao Leito/organização & administração , Eficiência Organizacional , Humanos , Modelos de Enfermagem , Pesquisa em Avaliação de Enfermagem , Registros de Enfermagem , Avaliação de Programas e Projetos de Saúde , Qualidade da Assistência à Saúde/organização & administração , Gestão da Qualidade Total/organização & administração , Estados Unidos
18.
Mol Genet Genomic Med ; 8(8): e1318, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32511891

RESUMO

BACKGROUND: Cornelia de Lange syndrome (CdLS) comprises a recognizable pattern of multiple congenital anomalies caused by variants of the DNA cohesion complex. Affected individuals may display a wide range of phenotypic severity, even within the same family. METHODS: Exome sequencing and confirmatory Sanger sequencing showed the same previously described p.Arg629Ter NIPBL variant in two half-brothers affected with CdLS. Clinical evaluations were obtained in a pro bono genetics clinic. RESULTS: One brother had relatively mild proportionate limb shortening; the other had complete bilateral hypogenesis of the upper arm with absence of lower arm structures, terminal transverse defects, and no digit remnants. His complex lower limb presentation included long bone deficiency and a deviated left foot. The mother had intellectual disability and microcephaly but lacked facial features diagnostic of the CdLS. CONCLUSION: We describe a collaboration between a pediatrics team from a resource-limited nation and USA-based medical geneticists. Reports describing individuals of West Indian ancestry are rarely found in the medical literature. Here, we present a family of Afro-Caribbean ancestry with CdLS presenting with phenotypic variability, including unusual lower limb abnormalities. The observation of this novel family adds to our knowledge of the phenotypic and molecular aspects of CdLS.


Assuntos
Síndrome de Cornélia de Lange/genética , Fenótipo , Adulto , Proteínas de Ciclo Celular/genética , Criança , Síndrome de Cornélia de Lange/diagnóstico , Feminino , Testes Genéticos , Humanos , Masculino , Mutação , Linhagem , Sequenciamento do Exoma
19.
Artigo em Inglês | MEDLINE | ID: mdl-31565539

RESUMO

Background: Dystonia is a relatively common feature of spinocerebellar ataxia 3 (SCA3). Childhood onset of SCA3 is rare and typically associated with either relatively large, or homozygous, CAG repeat expansions. Case report: We describe a 10-year-old girl with SCA3, who presented with tongue dystonia in addition to limb dystonia and gait ataxia due to a heterozygous expansion of 84 repeats in ATXN3. Discussion: Diagnosis of the SCAs can be challenging, and even more so in children. Tongue dystonia has not previously been documented in SCA3.


Assuntos
Distonia/fisiopatologia , Transtornos Neurológicos da Marcha/fisiopatologia , Doença de Machado-Joseph/fisiopatologia , Língua/fisiopatologia , Idade de Início , Ataxina-3/genética , Criança , Distonia/etiologia , Feminino , Transtornos Neurológicos da Marcha/etiologia , Humanos , Doença de Machado-Joseph/complicações , Doença de Machado-Joseph/genética , Proteínas Repressoras/genética , Expansão das Repetições de Trinucleotídeos/genética
20.
Br J Haematol ; 140(4): 385-93, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18162124

RESUMO

Mantle cell lymphoma (MCL) is associated with high relapse rates and poor survival when treated with conventional chemotherapy, with or without rituximab. We report the long-term follow-up of a phase II clinical trial using a new intensive multiagent chemotherapeutic regimen [cyclophosphamide, teniposide, doxorubicin and prednisone (CTAP) alternating with vincristine and high-dose methotrexate and cytarabine (VMAC)] in newly diagnosed MCL. Following 4-6 cycles of CTAP/VMAC induction, patients aged < or =65 years proceeded to consolidative autologous haematopoietic stem cell transplantation (auto-HSCT), while patients < or =55 years who had a HLA-identical sibling received allogeneic-HSCT (busulfan/cyclophosphamide conditioning for both). Twenty-five untreated MCL patients enrolled on the protocol between 1997 and 2002. Among evaluable patients, overall response rate (ORR) was 74% following induction chemotherapy. Seventeen patients received HSCT (autologous-13/allogeneic-4). On intent-to-treat analysis, ORR for patients who received consolidative HSCT was 100% (complete remission 76%). Therapy was well-tolerated with 4% treatment-related mortality (including HSCT). The 5-year event-free-survival (EFS) and overall survival (OS) for all patients was 35% and 50% respectively. Furthermore, at 66-months median follow-up, the 5-year EFS and OS for patients who received consolidative auto-HSCT was 54% and 75% respectively. Patients who received auto-HSCT had improved outcomes compared to no auto-HSCT (EFS P = 0.001; OS P = 0.0002). CTAP/VMAC induction followed by consolidative auto-HSCT for newly diagnosed MCL is associated with high ORR and durable survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Célula do Manto/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Métodos Epidemiológicos , Feminino , Humanos , Interferon-alfa/uso terapêutico , Interleucina-2/uso terapêutico , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Resultado do Tratamento
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