The Spanish Familial Pancreatic Cancer Registry (PANGENFAM): a decade follow-up of individuals at high-risk for pancreatic cancer.

The Spanish Familial Pancreatic Cancer Registry (PANGENFAM) was established in 2009 and aims to characterize the genotype and phenotype of familial pancreatic cancer (FPC). Furthermore, an early detection screening program for pancreatic ductal adenocarcinoma (PDAC) is provided to healthy high-risk individuals from FPC and hereditary pancreatic cancer families (first-degree relatives). This article describes our experience over the last 10 years in high-risk screening. Hereditary and familial pancreatic cancer families were identified through the oncology and gastroenterology units. High-risk individuals underwent annual screening with endoscopic ultrasound (EUS) and magnetic resonance (MRI) from age 40 or 10 years younger than the youngest affected family member. Results: PANGENFAM has enrolled 290 individuals from 143 families, including 52 PDAC cases and 238 high-risk individuals. All high-risk individuals eligible for screening were offered to enter the surveillance program, with 143 currently participating. Pancreatic abnormalities were detected in 94 individuals (median age 53 years (29-83), with common findings including cystic lesions and inhomogeneous parenchyma. Imaging test concordance was 66%. Surgical intervention was performed in 4 high-risk individuals following highly suspicious lesions detected by imaging. PANGENFAM is a valuable resource for science innovation, such as biobanking, with clinical and imaging data available for analysis. For high-risk families, it may offer a potential for early diagnosis. Collaboration with other national and international registries is needed to increase our understanding of the disease biology and to standardize criteria for inclusion and follow-up, optimizing cost-effectiveness and efficacy.

The best linear unbiased prediction (BLUP) method as a tool to estimate the lifetime risk of pancreatic ductal adenocarcinoma in high-risk individuals with no known pathogenic germline variants.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the Western world. The number of diagnosed cases and the mortality rate are almost equal as the majority of patients present with advanced disease at diagnosis. Between 4 and 10% of pancreatic cancer cases have an apparent hereditary background, known as hereditary pancreatic cancer (HPC) and familial pancreatic cancer (FPC), when the genetic basis is unknown. Surveillance of high-risk individuals (HRI) from these families by imaging aims to detect PDAC at an early stage to improve prognosis. However, the genetic basis is unknown in the majority of HRIs, with only around 10-13% of families carrying known pathogenic germline mutations. The aim of this study was to assess an individual's genetic cancer risk based on sex and personal and family history of cancer. The Best Linear Unbiased Prediction (BLUP) methodology was used to estimate an individual's predicted risk of developing cancer during their lifetime. The model uses different demographic factors in order to estimate heritability. A reliable estimation of heritability for pancreatic cancer of 0.27 on the liability scale, and 0.07 at the observed data scale as obtained, which is different from zero, indicating a polygenic inheritance pattern of PDAC. BLUP was able to correctly discriminate PDAC cases from healthy individuals and those with other cancer types. Thus, providing an additional tool to assess PDAC risk HRI with an assumed genetic predisposition in the absence of known pathogenic germline mutations.

Influence of Inflammation on Assessing Iron-Deficiency Anemia in Cuban Preschool Children.

INTRODUCTION: Anemia is a public health problem worldwide and is most prevalent in preschool children, for whom it is the most frequent cause of nutritional deficits. In turn, iron deficiency is the main cause of anemia, affecting 43% of children globally. Previous studies in Cuba show rates of iron deficiency in preschool children between 38.6% and 57.6%, higher in infants (71.2% to 81.1%). WHO recommends using serum ferritin as an indicator of iron deficiency accompanied by acute (C-reactive protein) and chronic (a1-acid glycoprotein) inflammation biomarkers. OBJECTIVE: Assess how inflammation affects measuring and reporting of iron-deficiency anemia rates in Cuban preschool children. METHODS: Data were obtained from serum samples contained in the National Anemia and Iron Deficiency Survey, and included presumably healthy preschool Cuban children (aged 6-59 months). Serum samples were collected from 1375 children from randomly selected provinces in 4 regions of the country from 2014 through 2018. We examined the association between ferritin and two inflammatory biomarkers: C-reactive protein and a1-acid glycoprotein. Individual inflammation-adjusted ferritin concentrations were calculated using four approaches: 1) a higher ferritin cut-off point (⟨30 g/L); 2) exclusion of subjects showing inflammation (C-reactive protein ⟩5 mg/L or a1-acid glycoprotein ⟩1 g/L); 3) mathematical correction factor based on C-reactive protein or a1-acid glycoprotein; and 4) correction by regression with the method proposed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia Group. We estimated confidence intervals of differences between unadjusted prevalence and prevalence adjusted for inflammation by each method. RESULTS: The proportion of children with inflammation according to C-reactive protein concentrations >5 mg/L was lower (11.1%, 153/1375) than the proportion measured according to the concentrations of a1-acid glycoprotein, at >1 g/L (30.8%, 424/1375). The percentage of children with high concentrations of at least one of the aforementioned biomarkers was 32.7% (450/1375). Thus, each correction method increased the observed prevalence of iron deficiency compared to unadjusted estimates (23%, 316/1375). This increase was more pronounced when using the internal regression correction method (based only on C-reactive protein) or the method based on a higher cut-off point. Adjustment using all four methods changed estimated iron deficiency prevalence, increasing it from 0.1% to 8.8%, compared to unadjusted values. CONCLUSIONS: One-third of preschool children had biomarkers indicating elevated inflammation levels. Without adjusting for inflammation, iron deficiency prevalence was underestimated. The significant disparity between unadjusted and inflammation-adjusted ferritin when using some approaches highlights the importance of selecting the right approach for accurate, corrected measurement. The internal regression correction approach is appropriate for epidemiological studies because it takes into account inflammation severity. However, other models should be explored that account for inflammation and also provide better adjusted ferritin concentrations.

Protective effect of the medicinal herb infusion "horchata" against oxidative damage in cigarette smokers: An ex vivo study.

Cigarette smoking has been associated with an increase in oxidative stress (OS) and is considered a predisposing factor to chronic noncommunicable diseases, whilst dietary antioxidants has been proposed as an alternative to cope with this oxidative stress. In this study, 20 smokers and 20 non-smokers were studied with the aim of determining their antioxidant status, as well as the ability of an infusion of 23 medicinal plants, to counteract the damage caused by OS. The plasma, red blood cells (RBCs) and polymorphonuclear cells (PBMCs) of both groups were incubated or not with the horchata infusion extract and then the OS markers, genotoxicity, nanostructure of RBCs membrane and genes related to oxidative responses and cellular functionality were evaluated. Up to 33 different compounds, mainly quercetin glycosides, were identified in the extract. A significant deterioration in the antioxidant status in smokers compared to non-smokers was found. The horchata infusion extract improved the nanostructure of RBCs and DNA damage, as well as the activity of the endogenous antioxidant enzymes and markers of oxidative damage to lipid, and proteins in plasma, RBCs and PBMCs in both groups, whilst no significant changes were found in the expression of different genes related to OS response.

VITAL phase 2 study: Upfront 5-fluorouracil, mitomycin-C, panitumumab and radiotherapy treatment in nonmetastatic squamous cell carcinomas of the anal canal (GEMCAD 09-02).

AIM: VITAL, a phase II single-arm study, aimed to evaluate efficacy and safety of panitumumab addition to 5-fluorouracil (5-FU), mitomycin-C (MMC) and radiotherapy (RT) in patients with localized squamous cell carcinoma of the anal canal (SCCAC). METHODS: Adult, treatment-naïve SCCAC patients (Stage T2-T4, any N, M0) and ECOG-PS ≤2, received panitumumab (6 mg/kg, day 1 and Q2W; 8 weeks), 5-FU (1000 mg/m2 /d, days 1-4 and 29-32), MMC (10 mg/m2 , days 1 and 29) and RT 45 Gy (1.8 Gy/fraction) to the primary tumor and mesorectal, iliac and inguinal lymph nodes, plus 10-15 Gy boost dose to the primary tumor and affected lymph nodes. The primary objective was disease free survival rate (DFS) at 3-years (expected 3-year DFS rate: 73.7 ± 12%). RESULTS: Fifty-eight patients (31 women; median age: 59 years; ECOG-PS 0-1:98%; TNM II [29%] (T2 or T3/N0/M0)/IIIA (T1-T3/N1/M0 or T4/N0/M0) [21%]/IIIB (T4/N1/M0 or any T/N2 or N3/M0) [47%]/nonevaluable [4%]) were included. The median follow-up was 45 months. The 3-year DFS rate was 61.1% (95% CI: 47.1, 72.4). The 3-year overall survival rate was 78.4% (95% CI: 65.1, 87.1). Eighteen patients (31.0%) required a colostomy within 2 years posttreatment. Grade 3-4 toxicities were experienced by 53 (91%) patients. Most common grade 3-4 treatment-related events were radiation skin injury (40%) and neutropenia (24%). No toxic deaths occurred. Improved efficacy in colostomy-free survival and complete response rate was observed in human papilloma virus positive patients. CONCLUSIONS: Panitumumab addition to MMC-5FU regimen in SCCAC patients increases toxicity and does not improve patients' outcomes. RT plus MMC-5FU remains the standard of care for localized SCCAC patients.

The Role of Iron Status in the Early Progression of Metronidazole Resistance in Trichomonas vaginalis Under Microaerophilic Conditions.

Trichomonas vaginalis is the etiological agent of human trichomoniasis. Metronidazole has high treatment success rate among trichomoniasis patients. However, metronidazole-resistant T. vaginalis has been reported, contributing in an increasing number of refractory cases. The mechanism of metronidazole resistance in this parasite is still unclear. In the vaginal environment, where the microaerophilic conditions prevail but the iron concentration is constantly fluctuating, the metronidazole resistance profile of T. vaginalis could be altered. In this study, we developed metronidazole-resistant strains of T. vaginalis and evaluate if iron availability is important to the action of the drug. The modulation of iron levels and iron chelation affected the actions of metronidazole both in susceptible and resistant strains. Interestingly, the early resistant strains exhibited minor iron content. The results of transcription analysis in the early resistant strains showed dysregulation in the expression of genes that codified proteins involved in iron transporter, iron-sulfur cluster assemblage, and oxidative stress response, which could not be observed in the late resistant and susceptible strains. Our results indicate that iron content plays an important role in the metronidazole action in T. vaginalis and likely to be related to iron-sulfur proteins involved in metronidazole activation and oxidative stress via Fenton reaction.

Arginine kinase shows nucleoside diphosphate kinase-like activity toward deoxythymidine diphosphate.

Arginine kinase (AK) (ATP: L-arginine phosphotransferase, E.C. 2.7.3.3) catalyzes the reversible transfer of ATP γ-phosphate group to L-arginine to synthetize phospho-arginine as a high-energy storage. Previous studies suggest additional roles for AK in cellular processes. Since AK is found only in invertebrates and it is homologous to creatine kinase from vertebrates, the objective of this work was to demonstrate nucleoside diphosphate kinase-like activity for shrimp AK. For this, AK from marine shrimp Litopenaeus vannamei (LvAK) was purified and its activity was assayed for phosphorylation of TDP using ATP as phosphate donor. Moreover, by using high-pressure liquid chromatography (HPLC) the phosphate transfer reaction was followed. Also, LvAK tryptophan fluorescence emission changes were detected by dTDP titration, suggesting that the hydrophobic environment of Trp 221, which is located in the top of the active site, is perturbed upon dTDP binding. The kinetic constants for both substrates Arg and dTDP were calculated by isothermal titration calorimetry (ITC). Besides, docking calculations suggested that dTDP could bind LvAK in the same cavity where ATP bind, and LvAK basic residues (Arg124, 126 and 309) stabilize the dTDP phosphate groups and the pyrimidine base interact with His284 and Ser122. These results suggest that LvAK bind and phosphorylate dTDP being ATP the phosphate donor, thus describing a novel alternate nucleoside diphosphate kinase-like activity for this enzyme.

Residuos agroindustriales con potencial para la producción de metano mediante la digestión anaerobia / Agroindustrial wastes methanization and bacterial composition in anaerobic digestion

Las toneladas de residuos orgánicos que se generan anualmente en la agroindustria pueden aprovecharse como materia prima para la producción de metano. Para que los residuos orgánicos se puedan convertir a metano a gran escala, es importante que previamente se realicen sobre ellos pruebas de biodegradabilidad; un parámetro importante que conviene establecer es su potencial bioquímico de metano. En el presente trabajo se estudió la biodegradabilidad, la producción de metano y el comportamiento de poblaciones de eubacterias y arqueobacterias durante la digestión anaerobia de residuos de plátano, mango y papaya provenientes de la agroindustria, adicionando un inóculo microbiano. Los residuos de mango y plátano tenían mayor contenido de materia orgánica (94 y 75 %, respectivamente) que el residuo de papaya con base en su relación sólidos volátiles/sólidos totales. Después de 63 días de tratamiento, la mayor producción de metano se observó en la digestión anaerobia del residuo de plátano: 63,89 ml de metano por g de demanda química de oxígeno del residuo. Los resultados del potencial bioquímico de metano demostraron que el residuo de plátano tiene el mejor potencial para ser usado como materia prima en la producción de metano. A través de un análisis por PCR-DGGE con oligonucleótidos específicos se logró evaluar el tamaño y la composición de las poblaciones de eubacterias y arqueobacterias presentes en la digestión anaerobia de residuos agroindustriales a lo largo del proceso.

The tons of organic waste that are annually generated by agro-industry, can be used as raw material for methane production. For this reason, it is important to previously perform biodegradability tests to organic wastes for their full scale methanization. This paper addresses biodegradability, methane production and the behavior of populations of eubacteria and archaeabacteria during anaerobic digestion of banana, mango and papaya agroindustrial wastes. Mango and banana wastes had higher organic matter content than papaya in terms of their volatile solids and total solid rate (94 and 75 % respectively). After 63 days of treatment, the highest methane production was observed in banana waste anaerobic digestion: 63.89 ml CH4/per gram of chemical oxygen demand of the waste. In the PCR-DGGE molecular analysis, different genomic footprints with oligonucleotides for eubacteria and archeobacteria were found. Biochemical methane potential results proved that banana wastes have the best potential to be used as raw material for methane production. The result of a PCR- DGGE analysis using specific oligonucleotides enabled to identify the behavior of populations of eubacteria and archaeabacteria present during the anaerobic digestion of agroindustrial wastes throughout the process.

A novel viral thymidylate kinase with dual kinase activity.

Nucleotide phosphorylation is a key step in DNA replication and viral infections, since suitable levels of nucleotide triphosphates pool are required for this process. Deoxythymidine monophosphate (dTMP) is produced either by de novo or salvage pathways, which is further phosphorylated to deoxythymidine triphosphate (dTTP). Thymidyne monophosphate kinase (TMK) is the enzyme in the junction of both pathways, which phosphorylates dTMP to yield deoxythymidine diphosphate (dTDP) using adenosine triphosphate (ATP) as a phosphate donor. White spot syndrome virus (WSSV) genome contains an open reading frame (ORF454) that encodes a thymidine kinase and TMK domains in a single polypeptide. We overexpressed the TMK ORF454 domain (TMKwssv) and its specific activity was measured with dTMP and dTDP as phosphate acceptors. We found that TMKwssv can phosphorylate dTMP to yield dTDP and also is able to use dTDP as a substrate to produce dTTP. Kinetic parameters K M and k cat were calculated for dTMP (110 µM, 3.6 s(-1)), dTDP (251 µM, 0.9 s(-1)) and ATP (92 µM, 3.2 s(-1)) substrates, and TMKwssv showed a sequential ordered bi-bi reaction mechanism. The binding constants K d for dTMP (1.9 µM) and dTDP (10 µM) to TMKwssv were determined by Isothermal Titration Calorimetry. The affinity of the nucleotidic analog stavudine monophosphate was in the same order of magnitude (K d 3.6 µM) to the canonical substrate dTMP. These results suggest that nucleotide analogues such as stavudine could be a suitable antiviral strategy for the WSSV-associated disease.

Beneficial effects of a flavanol-enriched cacao beverage on anthropometric and cardiometabolic risk profile in overweight subjects / Efectos beneficiosos de una bebida de cocoa enriquecida con flavanol en el perfil antropométrico y de riesgo cardiometabólico en sujetos con sobrepeso

Overweight and obesity are associated with systemic inflammation and oxidative stress which, in turn, enhance the development of cardiometabolic disruptions. Lifestyle changes and pharmacologic approaches show moderately effective results regarding overall health improvements. Evidence suggests that cacao flavonoids are associated with a reduced cardiometabolic risk, due to the modulation of molecular pathways subjacent to glucose and lipids metabolism. The aim of this study was to assess the effects of cacao flavonoids supplementation on anthropometric and cardiometabolic risk factors in overweight subjects. A double-blind, placebo-controlled, pilot clinical trial was conducted in overweight subjects with borderline criteria of metabolic syndrome. Participants were randomly assigned to either, supplement of cacao flavonoids (80 mg) or placebo, daily, for 4 weeks. Cardiometabolic variables were blood pressure, glycemia and lipid profile. Serum markers of oxidative damage (free protein carbonyls and malondialdehyde) were also analyzed. Anthropometric measurements included body weight, body mass index, waist circumference, and fat and fat-free mass. We found significant reductions in body weight (p = 0.04), waist circumference (p = 0.03), triacylglycerols (p < 0.01), TG/HDL ratio (p = 0.01), MDA (p = 0.02) and protein carbonyls (p = 0.01) in the flavonoid-supplemented group. Results from this study show that cacao flavonoids can effectively modulate anthropometric and cardiometabolic risk factors.

El sobrepeso y la obesidad están asociados con la inflamación sistémica y el estrés oxidativo, que, a su vez, incrementan el desarrollo de trastornos cardiometabólicos. Cambios en el estilo de vida y tratamientos farmacológicos muestran resultados moderadamente eficaces en relación con la mejora general de la salud. La evidencia sugiere que los flavonoides del cacao se asocian con un riesgo cardiometabólico reducido, debido a la modulación de las vías moleculares subyacentes al metabolismo de la glucosa y de los lípidos. El objetivo de este estudio fue evaluar los efectos de la suplementación de flavonoides del cacao sobre factores de riesgo cardiometabólico y antropométrico en sujetos con sobrepeso. Se llevó a cabo un ensayo clínico piloto, doble ciego y controlado con placebo en sujetos con sobrepeso y criterios limítrofes de síndrome metabólico. Los participantes fueron asignados al azar a cuatro semanas de tratamiento con suplemento oral de flavonoides de cacao (80 mg) diario o placebo. Las variables cardiometabólicas analizadas fueron presión arterial sistémica, glicemia y perfil lipídico. También se analizaron los marcadores séricos de estrés oxidativo (carbonilos proteicos libres y malondialdehído). Las medidas antropométricas incluyeron el peso corporal, índice de masa corporal, circunferencia de la cintura, masa grasa y masa libre de grasa. Se encontró una reducción significativa en el peso corporal (p = 0.04), circunferencia de la cintura (p = 0.03), triglicéridos (p < 0.01), la relación TG/HDL (p = 0.01), MDA (p = 0.02) y carbonilos (p = 0.01) en el grupo con suplemento de flavonoides. Los resultados de este estudio muestran que los flavonoides del cacao pueden modular efectivamente factores de riesgo cardiometabólico y antropométricos.

Coronary flow velocity reserve during pharmacologic stress echocardiography with normal contractility adds important prognostic value in diabetic and nondiabetic patients.

BACKGROUND: Coronary flow velocity reserve (CFVR) increases the diagnostic sensitivity of stress echocardiography. The aim of this study was to evaluate the prognostic value of CFVR in patients without new wall motion abnormalities during pharmacologic stress echocardiography. METHODS: The outcomes of 651 patients with normal wall motion response during stress echocardiography with dobutamine up to 50 µg/kg/min (n = 351) or dipyridamole up to 0.84 mg/kg over 4 min (n = 300) were evaluated. CFVR was calculated simultaneously in the distal territory of the left anterior descending coronary artery. CFVR ≥ 2 was defined as normal. Major events considered during follow-up were cardiovascular death, myocardial infarction, and late myocardial revascularization. RESULTS: Normal CFVR was recorded in 523 patients and reduced CFVR in 128. During a mean follow-up period of 34.6 ± 18 months, 48 major events occurred, in 25 patients (4.8%) with normal and 23 patients (18%) with reduced CFVR; event-free survival was significantly different between patients with normal versus abnormal CFVR (P < .0001). Diabetes increased risk only in patients with abnormal CFVR (P = .05). In the multivariate analysis, CFVR and history of smoking were the only independent predictors of combined morbidity and mortality. Abnormal CFVR was associated with a higher event rate, independently of the pharmacologic stress technique used. The event hazard ratio was inversely proportional to CFVR. CONCLUSIONS: CFVR was an independent predictor of mortality after pharmacologic stress echocardiography with normal wall motion, and the degree of decrease was associated with increased risk. Diabetes worsened prognosis only with abnormal CFVR.

Tratamiento preventivo de la enfermedad tromboembolica venosa en pacientes afectados por fractura de cadera / Preventive treatment of venous thromboembolic illness in patiets affected by hip fracture

Se realiza una revisión de la frecuencia de enfermedad tromboenbólica venosa en la fractura de cadera resaltando la importancia de esta alta frecuencia en trombosis venosa profunda y embolia pulmonar. Se dan a conocer los distintos tratamientos tanto no farmacológicos como farmacológicos utilizados a nivel internacional. Se propone un protocolo de actuación para el tratamiento preventivo de la enfermedad tromboembólica venosa en nuestro medio.

Helicobacter pylori en niños menores de 2 años de edad aparentemente sanos o afectados por diarreas crónicas / Helicobacter pylori in children apparently healthy or affected with chronic diarrheas

El porcentaje de infestación por Helicobacter pylori (Hp), medido mediante inmunoensayo cromatográfico fue muy elevado en niños menores de 2 años de edad atendidos por diarreas crónicas en dos hospitales pediátricos, o total en niños aparentemente sanos de un municipio de Ciudad de La Habana. En una muestra seleccionada al azar casi la totalidad de ellos mostró anticuerpos para esta bacteria. Los niños afectados de diarreas crónicas manifestaron un mayor porcentaje de antecedentes patológicos personales o familiares de parasitismo, giardiasis, gastritis, úlcera, estomatitis, glositis y otras manifestaciones clínicas con posible relación causal con la infección por Hp. A pesar de la función favorecedora de la hipoclorhidria posinfección, la elevada infestación por Hp tanto en niños enfermos como sanos no permite establecer asociaciones entre diarrea e infección por esta bacteria. La presencia de anticuerpos no es indicativo de infección activa. El diagnóstico confirmatorio en niños de esa edad debe realizarse por métodos isotópicos

Análisis genético de las fisuras faciales humanas. Reevaluación del tipo de herencia: poligénica o monogénica / Genetic analysis of human the face fissures

Analiza que las fisuras labio palatinas constituyen una de las malformaciones congénitas más frecuentes en nuestro medio. Uno de los objetivos de este trabajo es conocer la relación entre la severidad de la afección y el sexo del individuo; grado de severidad y antecedentes familiares y heredabilidad con el grado de parentesco. Para el análisis se tomó en cuenta las fisuras palatinas como entidad propia y las fisuras labiales con o sin fisura palatina como otra entidad. Se analizó la genealogía de los individuos afectos hasta el tercer grado de parentesco. Se estudiaron 60 familias con un total de 62 individuos afectos: 30 con fisura palatina, 27 con fisura labio-palatina y 5 con fisura labial. Se buscó la asociación de estos casos con otro tipo de malformaciones y síndromes, así como la relación entre el tipo de fisura con alteraciones cromosómicas específicas. Este estudio hace pensar en primera instancia en un tipo de herencia monogénica dominante, pues se ve un patrón de transmisión vertical, sin embargo la alteración no se presenta en todas las generaciones como es de esperarse tratándose de una herencia dominante, lo que haría pensar en una herencia poligénica, donde la expresión variable de un grupo de genes desencadenarían los diferentes tipos de fisuras existentes. De esta manera se descarta también un patrón de herencia recesiva, pues no existe un comportamiento de transmisión en este sentido.

Registro nacional colaborativo de alteraciones y variantes cromosómicas humanas. Informe Actualizado 1992

Una de las metas más importantes para los profesionales que trabajan en Genética Médica, es conocer la incidencia y la frecuencia de alteraciones y variantes cromosómicas en un área determinada, para planificar acciones genéticas comunitarias. Hemos recopilado los datos de autosomopatías, gonosomopatías, variantes y polimorfismos cromosómicos, sobre un total de 869 cariotipos la mayoría con alteraciones y variantes, en lo que pretendemos sea el Registro Nacional Colaborativo de Alteraciones y Variantes Cromosómicas Humanas (RNCAVCH), para la conformación del Registro se han seguido las normas internacionales del Repository of Human Chromosomal Variants and Anomalies: An International Registry of Abnormal Karyotypes (Delaware-USA); nuestros resultados recopilados hasta la fecha, constan ya en este registro. Los datos han sido obtenidos por comunicación personal y voluntaria de los investigadores, recopilación de la literatura científica nacional y de la base de datos de algunas Instituciones que tienen Servicios de Genética. Los datos podrán ser ampliados y requeridos por los investigadores interesados en Genética.