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1.
Int J Dermatol ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38955474

RESUMEN

BACKGROUND: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder (PCSM-LPD) is an increasingly recognized entity with heterogeneous management strategies that may include radiotherapy. OBJECTIVE: Our aim was to characterize treatment options for PCSM-LPD, with a focus on the role of radiotherapy. METHODS: This is a retrospective review of 46 patients seen in the Cutaneous Lymphoma Program at the University of Texas MD Anderson Cancer Center, with a clinicopathologic review consistent with PCSM-LPD. All patients were biopsied and underwent observation, topical/intralesional steroids, and/or radiotherapy. Patients were confirmed to have residual disease prior to radiotherapy. RESULTS: All patients achieved a complete response (CR). Sixteen patients (35%) received focal radiotherapy, with a CR in 15 (94%). The CR rate following ultra-low-dose radiotherapy (4 Gy in 1-2 fractions) was 92%. There was no grade 3 toxicity after radiotherapy. Thirty patients were managed without radiotherapy, with excision and observation or steroids. CONCLUSION: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder has excellent outcomes, and management strategies may include observation following biopsy, steroids, or radiation. Ultra-low-dose radiotherapy results in excellent outcomes with limited toxicity and is effective for persistent lesions after steroidal therapy.

3.
Bol Med Hosp Infant Mex ; 82(Supl 1): 1-13, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39009030

RESUMEN

INTRODUCTION: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing. METHOD: A consensus was reached with experts in the field of inborn errors of metabolism (EIM), including eight pediatric gastroenterologists, two EIM specialists, two geneticists, three pediatric nutritionists specialized in EIM, and a pediatric surgeon specializing in transplants. Six working groups were tasked with formulating statements and justifications, and 32 statements were anonymously voted on using the Likert scale and the Delphi method. The first virtual vote achieved an 80% consensus, with the remaining 20% determined in person. RESULTS: The statements were categorized into epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counseling. CONCLUSIONS: This consensus serves as a valuable tool for primary care physicians, pediatricians, and pediatric gastroenterologists, aiding in the prompt diagnosis and treatment of this disease. Its impact on the morbidity and mortality of patients with tyrosinemia type 1 is substantial.


INTRODUCCIÓN: La tirosinemia tipo 1 es una enfermedad rara, con herencia autosómica recesiva, con múltiples manifestaciones clínicas, que pueden comprender desde falla hepática aguda neonatal, síndrome colestásico neonatal, hepatitis crónica, cirrosis o hepatocarcinoma, hasta alteraciones renales como acidosis tubular renal, síndrome de Fanconi o raquitismo hipofosfatémico, entre otras. El diagnóstico se basa en la presencia de metabolitos tóxicos en la sangre y la orina, idealmente con la confirmación molecular de la enfermedad. MÉTODO: Se realizó un consenso con expertos en el área de los errores innatos del metabolismo (EIM): ocho gastroenterólogos pediatras, dos médicos especialistas en EIM, dos genetistas, tres nutriólogas pediatras especializadas en EIM y un cirujano pediatra especialista en trasplantes. Se formaron seis mesas de trabajo encargadas de desarrollar los enunciados con sus justificaciones y fueron votados anónimamente 32 enunciados en una escala Likert con un método Delphi. La primera votación fue virtual, obteniendo consenso del 80% de los enunciados, y la segunda fue presencial, obteniendo el 20% restante. RESULTADOS: Los enunciados fueron divididos en epidemiología, cuadro clínico, diagnóstico, tratamiento nutricional y médico, y consejo genético. CONCLUSIONES: Este consenso constituye una valiosa herramienta para los médicos de atención primaria, pediatras y gastroenterólogos pediátricos, ya que ayuda a diagnosticar y tratar rápidamente esta enfermedad. Su impacto en la morbilidad y mortalidad de los pacientes con tirosinemia tipo 1 es sustancial.


Asunto(s)
Consenso , Tirosinemias , Humanos , Tirosinemias/diagnóstico , Tirosinemias/terapia , México , Recién Nacido , Técnica Delphi , Asesoramiento Genético
4.
Am J Clin Pathol ; 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38946194

RESUMEN

OBJECTIVES: We sought to investigate the morphologic and immunophenotypic characteristics of TCL1 family-negative T-cell prolymphocytic leukemia (T-PLL). METHODS: Twenty cases of TCL1 family-negative T-PLL were studied. RESULTS: The doubling time of leukemic cells ranged from less than 2 days to more than 5 years, with a median of 5.5 months. Leukemic cells were small to medium-sized, with round to irregular nuclei, variably condensed chromatin, and small amounts of agranular cytoplasm. A visible nucleolus was identified in 11 (55%) cases. Cytoplasmic blebs/protrusions were identified in all cases, but their occurrence was highly variable from case to case. Bone marrow biopsy showed an interstitial pattern in 90% of cases and a diffuse pattern in the remaining 10% of cases. Flow cytometric immunophenotypic analysis showed that the leukemic cells in all cases were CD4 positive; 3 (15%) also showed concurrent CD8 expression. All cases were positive for CD2 and CD5. Surface CD3 and CD7 were positive in 19 of 20 (95%) cases, and all CD3-positive cases expressed the T-cell receptor αß. Compared with prototypic T-PLL cases, these 2 groups shared many immunophenotypic findings, except CD8 and CD26, both of which were more commonly expressed in prototypic T-PLL cases. CONCLUSIONS: TCL1 family-negative T-PLL cases have morphologic and immunophenotypic features that are similar to prototypic T-PLL. They are characterized by neoplastic proliferation of small to medium-sized mature T cells with CD4-positive T-cell receptor αß phenotype. Tumor cells frequently maintain pan-T antigen expression. Recognizing these morphologic and immunophenotypic features will aid in accurately diagnosing this rare subset of T-PLL.

6.
Cancer Discov ; 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900051

RESUMEN

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR. We found that CD28, a costimulatory molecule not inherently present in mature NK cells, significantly enhanced the antitumor efficacy and long-term cytotoxicity of CAR-NK cells both in vitro and in multiple xenograft models of hematologic and solid tumors. Mechanistically, we showed that CD28 linked to CD3Z creates a platform that recruits critical kinases, such as LCK and ZAP70, initiating a signaling cascade that enhances CAR-NK cell function. Our study provides insights into how CD28 costimulation enhances CAR-NK cell function and supports its incorporation in NK-based CARs for cancer immunotherapy.

7.
Mol Psychiatry ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783055

RESUMEN

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of all patients. Of 4114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of potential actionability from genetic findings and/or phenoconversion. Genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.

8.
J Clin Med ; 13(8)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38673429

RESUMEN

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

9.
Blood Adv ; 8(14): 3825-3837, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38607394

RESUMEN

ABSTRACT: Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective analysis of patients with non-Hodgkin lymphoma (NHL) seen at MD Anderson Cancer Center (MDACC) to investigate the association between trial participation, race/ethnicity, travel distance, and neighborhood socioeconomic status (nSES). Using patient addresses, we ascertained nSES variables on educational attainment, income, poverty, racial composition, and housing at the census tract (CT) level. We also performed geospatial analysis to determine the geographic distribution of clinical trial participants and distance from patient residence to MDACC. We examined 3146 consecutive adult patients with NHL seen between January 2017 and December 2020. The study cohort was predominantly male and non-Hispanic White (NHW). The most common insurance types were private insurance and Medicare; only 1.1% of patients had Medicaid. There was a high overall participation rate of 30.5%, with 20.9% enrolled in therapeutic trials. In univariate analyses, lower participation rates were associated with lower nSES including higher poverty rates and living in crowded households. Racial composition of CT was not associated with differences in trial participation. In multivariable analysis, trial participation varied significantly by histology, and participation declined nonlinearly with age in the overall, follicular lymphoma, and diffuse large B-cell lymphoma (DLBCL) models. In the DLBCL subset, Hispanic patients had lower odds of participation than White patients (odds ratio, 0.36; 95% confidence interval, 0.21-0.62; P = .001). In our large academic cohort, race, sex, insurance type, and nSES were not associated with trial participation, whereas age and diagnosis were.


Asunto(s)
Ensayos Clínicos como Asunto , Linfoma no Hodgkin , Factores Socioeconómicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Linfoma no Hodgkin/terapia , Anciano , Adulto , Estudios Retrospectivos , Demografía , Clase Social , Características de la Residencia , Participación del Paciente , Características del Vecindario
11.
Arch Prev Riesgos Labor ; 27(1)2024 Jan 17.
Artículo en Español | MEDLINE | ID: mdl-38655605

RESUMEN

Un año más, mediante esta nota editorial, damos cuenta de las estadísticas y los principales avances de nuestra revista. En cuanto a las estadísticas editoriales, que se detallan en los apartados posteriores, podemos afirmar que son las de una revista consolidada: flujo nutrido y constante de trabajos recibidos/publicados, tasas de aceptación y rechazo proporcionadas, tiempos de gestión razonables y diversidad en las autorías. El logro más destacable del 2023 fue superar con éxito el proceso de evaluación de la Octava edición de Evaluación de la calidad editorial y científica de las revistas científicas españolas, comúnmente conocido como 'Sello FECYT'….


Asunto(s)
Publicaciones Periódicas como Asunto , Publicaciones Periódicas como Asunto/normas , España , Edición/normas
12.
Cancer Cell ; 42(4): 605-622.e11, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38458188

RESUMEN

SMARCA4 encodes one of two mutually exclusive ATPase subunits in the BRG/BRM associated factor (BAF) complex that is recruited by transcription factors (TFs) to drive chromatin accessibility and transcriptional activation. SMARCA4 is among the most recurrently mutated genes in human cancer, including ∼30% of germinal center (GC)-derived Burkitt lymphomas. In mice, GC-specific Smarca4 haploinsufficiency cooperated with MYC over-expression to drive lymphomagenesis. Furthermore, monoallelic Smarca4 deletion drove GC hyperplasia with centroblast polarization via significantly increased rates of centrocyte recycling to the dark zone. Mechanistically, Smarca4 loss reduced the activity of TFs that are activated in centrocytes to drive GC-exit, including SPI1 (PU.1), IRF family, and NF-κB. Loss of activity for these factors phenocopied aberrant BCL6 activity within murine centrocytes and human Burkitt lymphoma cells. SMARCA4 therefore facilitates chromatin accessibility for TFs that shape centrocyte trajectories, and loss of fine-control of these programs biases toward centroblast cell-fate, GC hyperplasia and lymphoma.


Asunto(s)
Haploinsuficiencia , Linfoma de Células B , Animales , Humanos , Ratones , Cromatina , ADN Helicasas/genética , Hiperplasia , Linfoma de Células B/genética , Proteínas Nucleares/genética , Factores de Transcripción/genética
13.
Hum Pathol ; 146: 1-7, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38460798

RESUMEN

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and p53 mutant pattern by immunohistochemistry. Comparative analysis disclosed that EZH2 expression correlates with high Ki-67 proliferation rate irrespective of TP53 mutation. Aggressive histology is associated with EZH2 expression or TP53 mutation, possibly via independent mechanisms. p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome.


Asunto(s)
Biomarcadores de Tumor , Proteína Potenciadora del Homólogo Zeste 2 , Linfoma de Células del Manto , Mutación , Proteína p53 Supresora de Tumor , Humanos , Proteína Potenciadora del Homólogo Zeste 2/genética , Proteína Potenciadora del Homólogo Zeste 2/análisis , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/mortalidad , Proteína p53 Supresora de Tumor/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Anciano de 80 o más Años , Adulto , Análisis Mutacional de ADN , Inmunohistoquímica , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Proliferación Celular
14.
Virchows Arch ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388965

RESUMEN

Acute myeloid leukemia (AML) is the most common acute leukemia in adults. While induction chemotherapy leads to remission in most patients, a significant number will experience relapse. Therefore, there is a need for novel therapies that can improve remission rates in patients with relapsed and refractory AML. CD70 is the natural ligand for CD27 (a member of the TNF superfamily) and appears to be a promising therapeutic target. Consequently, there is considerable interest in developing chimeric antigen receptor (CAR) T-cell therapy products that can specifically target CD70 in various neoplasms, including AML. In this study, we employed routine diagnostic techniques, such as immunohistochemistry and flow cytometry, to investigate the expression of CD70 in bone marrow samples from treatment-naïve and relapsed AML patients after hypomethylating agents (HMA). Also, we evaluated the impact of HMA on CD70 expression and examined CD70 expression in various leukemic cell subsets and normal hematopoietic progenitors.

15.
Epidemiol Infect ; 152: e12, 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38185825

RESUMEN

Salmonella enterica continues to be a leading cause of foodborne morbidity worldwide. A quantitative risk assessment model was developed to evaluate the impact of pathogen enumeration and serotyping strategies on public health after consumption of undercooked contaminated ground turkey in the USA. The risk assessment model predicted more than 20,000 human illnesses annually that would result in ~700 annual reported cases. Removing ground turkey lots contaminated with Salmonella exceeding 10 MPN/g, 1 MPN/g, and 1 MPN/25 g would decrease the mean number of illnesses by 38.2, 73.1, and 95.0%, respectively. A three-class mixed sampling plan was tested to allow the detection of positive lots above threshold levels with 2-6 (c = 1) and 3-8 samples per lot (c = 2) using 25-g and 325-g sample sizes for a 95% probability of rejecting a contaminated lot. Removal of positive lots with the presence of highly virulent serotypes would decrease the number of illnesses by 44.2-87.0%. Based on these model prediction results, risk management strategies should incorporate pathogen enumeration and/or serotyping. This would have a direct impact on illness incidence linking public health outcomes with measurable food safety objectives, at the cost of diverting production lots.


Asunto(s)
Salmonella enterica , Salmonella , Animales , Humanos , Serotipificación , Pavos , Gestión de Riesgos , Evaluación de Resultado en la Atención de Salud
16.
Med Educ ; 58(8): 952-960, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38273430

RESUMEN

INTRODUCTION: Medical residents may be required to handle health care management (HCM) tasks alongside their clinical duties, despite not having received training to perform them. However, little research has been done on how medical residents acquire HCM skills at the workplace and how these experiences impact their learning. METHODS: We completed a qualitative research study using the Constructivist Grounded Theory approach inform by the Figured World theory. To gather data, we held focus groups and conducted semi-structured interviews with 22 medical residents from various disciplines and learning levels at Pontificia Universidad Javeriana. We utilised iterative data collection and analysis, constant comparison methods and theoretical sampling to construct our findings. RESULTS: We constructed two different worlds to represent how residents acquire HCM skills: the non-managing physician and the physician-as-manager. The former was characterised by a discourse that underplayed the role of the HCM tasks as part of residents' training, was full of negative interactions with the health care team and limited residents' agency. In the latter, residents collaborated and learned from health care team members, had supervisors who modelled how to incorporate HCM tasks into daily activities and expanded residents' agency. Residents developed their professional identity according to the world they were introduced into. DISCUSSION: Educational leaders must understand that the non-managing physician figured world gives residents a feeling of uprooting and discomfort when carrying out this type of tasks. To transform this world into the physician-as-manager, it is necessary to reconfigure some workplace hierarchies, consolidate interprofessional collaborations and change the discourse perpetuated by influential role models. Supervisors must also strengthen their knowledge of HCM and improve its integration into clinical practice. Any effort to train residents on HCM competencies could be lost if the workplace underscores their value in patient care.


Asunto(s)
Teoría Fundamentada , Internado y Residencia , Investigación Cualitativa , Lugar de Trabajo , Humanos , Grupos Focales , Femenino , Masculino , Competencia Clínica , Adulto
17.
Am J Hematol ; 99(3): 408-421, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38217361

RESUMEN

To address the current and long-term unmet health needs of the growing population of non-Hodgkin lymphoma (NHL) patients, we established the Lymphoma Epidemiology of Outcomes (LEO) cohort study (NCT02736357; https://leocohort.org/). A total of 7735 newly diagnosed patients aged 18 years and older with NHL were prospectively enrolled from 7/1/2015 to 5/31/2020 at 8 academic centers in the United States. The median age at diagnosis was 62 years (range, 18-99). Participants came from 49 US states and included 538 Black/African-Americans (AA), 822 Hispanics (regardless of race), 3386 women, 716 age <40 years, and 1513 rural residents. At study baseline, we abstracted clinical, pathology, and treatment data; banked serum/plasma (N = 5883, 76.0%) and germline DNA (N = 5465, 70.7%); constructed tissue microarrays for four major NHL subtypes (N = 1189); and collected quality of life (N = 5281, 68.3%) and epidemiologic risk factor (N = 4489, 58.0%) data. Through August 2022, there were 1492 deaths. Compared to population-based SEER data (2015-2019), LEO participants had a similar distribution of gender, AA race, Hispanic ethnicity, and NHL subtype, while LEO was underrepresented for patients who were Asian and aged 80 years and above. Observed overall survival rates for LEO at 1 and 2 years were similar to population-based SEER rates for indolent B-cell (follicular and marginal zone) and T-cell lymphomas, but were 10%-15% higher than SEER rates for aggressive B-cell subtypes (diffuse large B-cell and mantle cell). The LEO cohort is a robust and comprehensive national resource to address the role of clinical, tumor, host genetic, epidemiologic, and other biologic factors in NHL prognosis and survivorship.


Asunto(s)
Linfoma no Hodgkin , Calidad de Vida , Humanos , Femenino , Estados Unidos/epidemiología , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Linfoma no Hodgkin/diagnóstico , Linfocitos B/patología , Pronóstico
19.
Pediatr Neurol ; 151: 68-72, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38113697

RESUMEN

BACKGROUND: Early infantile epileptic encephalopathy 25 (EIEE25) is a distinct type of neonatal epileptic encephalopathy caused by autosomal recessive mutations in the SLC13A5 gene. SLC13A5 encodes a transmembrane sodium/citrate cotransporter required for regulating citrate entry into cells. METHODS: Four families with recessively inherited epileptic encephalopathy were sequenced by clinically accredited laboratories using commercially available epilepsy gene panels. Patients were examined by a neurologist and were clinically diagnosed with infantile epileptic encephalopathy. RESULTS: We present four families with global developmental delay, intellectual disability, and defective tooth development with four novel homozygous mutations in SLC13A5. The neurological examination showed spastic quadriplegia with increased deep tendon reflexes. Brain magnetic resonance imaging showed nonspecific signal abnormality of the bilateral hemispheric white matter. Despite similar clinical features, the conditions were based on different molecular mechanisms acting on SLC13A5 (abnormal splicing, large-scale deletions, and tandem-residue insertion). CONCLUSIONS: Our results extend the landscape of autosomal recessive inherited homozygous mutations in SLC13A5 that cause a distinctive syndrome of severe neonatal epileptic encephalopathy. Our observations confirm the homogeneity of epileptic encephalopathy and dental abnormalities as a distinct clinical marker for EIEE25 despite the heterogeneous functional and mutational background.


Asunto(s)
Encefalopatías , Epilepsia , Espasmos Infantiles , Simportadores , Recién Nacido , Humanos , Espasmos Infantiles/diagnóstico por imagen , Espasmos Infantiles/genética , Espasmos Infantiles/patología , Epilepsia/genética , Encefalopatías/diagnóstico por imagen , Encefalopatías/genética , Mutación/genética , Síndrome , Ácido Cítrico , Simportadores/genética
20.
Pac Symp Biocomput ; 29: 322-326, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38160289

RESUMEN

The following sections are included:OverviewDealing with the lack of diversity in current research datasetsDevelopment of fair machine learning algorithmsRace, genetic ancestry, and population structureConclusionAcknowledgments.


Asunto(s)
Biología Computacional , Medicina de Precisión , Humanos , Aprendizaje Automático , Inequidades en Salud
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