Perfil protéomico en suero materno de embarazos con Síndrome de Down

El diagnóstico prenatal ha tomado una gran importancia en las últimas décadas proponiendo mejorías en los métodos de detección volviéndose más eficientes, seguros y precoces. La necesidad creciente en este campo se debe principalmente a que en la sociedad urbana actual los embarazos ocurren a edades mayores aumentando el riesgo de cromosomopatías por lo que la detección precoz y adecuada puede ayudar a tomar alguna decisión acerca de la continuación de la gestación o preparación de la familia y del personal médico para una mejor atención del producto. El síndrome de Down es la cromosomopatía autosómica más frecuente por lo que los esfuerzos realizados en el campo del diagnóstico prenatal son principalmente enfocados en la detección de fetos con esta afección la cual puede tener consecuencias en la salud del producto permitiendo ser detectadas y tratadas a tiempo como en caso de cardiopatías congénitas las cuales son prevalentes en este grupo de pacientes comparadas con la población en general. Las pruebas diagnósticas en esta área hasta el momento son pruebas invasivas las cuales conllevan riesgo para la madre y el producto además deben ser realizadas por personal capacitado, por lo cual se implementaron pruebas más seguras llamadas métodos no invasivos los cuales, aunque no son diagnósticos sino de tamizaje, han mejorado el índice de detección desde el basado en la edad materna hasta técnicas más sofisticadas como el DNA libre fetal o técnicas proteómicas todo esto con la finalidad de lograr una mejor selección de las pacientes sometidas a pruebas invasivas evitando procedimientos que pongan en riesgo innecesario al binomio madre-feto. La proteómica, siendo el más nuevo competidor en esta área, nos permite obtener un análisis detallado del perfil proteico de tejidos biológicos y fluidos en un momento y condición determinado y a partir de ello realizar una comparación entre condiciones fisiológicas normales y patológicas, por lo que en este estudio se pretende analizar tres grupos de mujeres con condiciones clave para determinar la utilidad de este método por medio de la identificación y cuantificación de proteínas para lograr demostrar una diferencia entre las condiciones protéicas durante el periodo de gestación en situación fisiológica o patológica de feto y usando de control interno mujeres no embarazadas

Spectrum of hemifacial microsomia in a pre-term newborn: case presentation and literature review

The spectrum of hemifacial microsomia, or facio-auriculo-vertebral spectrum, is a complex of craniofacial and vertebral anomalies. Axis malformation is microtia, more often on the right side of 3:2. It may be associated with mandibular hypoplasia and vertebral malformations. It is more frequent in males and in twin pregnancies. Clinical case: Newborn male, preterm, of 29.5 weeks gestational age, twin product, second twin pregnancy, dichorionic and diamniotic, born by cesarean section, which presented hemifacial microsomia, microtia of the left Tanzer 3 and the right auricle of low implantation with a backward rotation, left appendices and macrostomia. A thoracoabdominal X-ray found hemivertebrae in the cervical and dorsal area, which discussed genetic performing diagnosis of the hemifacial microsomia spectrum. An ear TAC is done, the bone atresia of the left ear meeting at the level of the left ear without evidence of tympanic membranes and with a dysplastic oscicular chain attached to the lateral wall of the attic. Discharged at 78 days of chronological age with 6 days of age, corrected with the consultation of neonatal high-risk follow-up. Conclusion: Facial asymmetry must be widely evaluated in patients with microtia, including deliberate search of renal, cardiac and spinal-level conditions, in order to diagnose pathologies such as the spectrum of hemifacial microsomia early

Spondylothoracic dysostosis, Jarcho Levin syndrome: case report

Dysostosis spondylothoracic, or Jarcho Levin syndrome, is characterized by a short neck and thorax, a protruding abdomen, abnormal vertebral segmentation and fusion posterior costal resulting in thoracic restriction or respiratory failure and scoliosis. The prevalence is estimated at 1 in 12,000 live births for the people of Puerto Rico and 1 per 200,000 for the rest of the world. It is inherited in an autosomal recessive manner and the only related gene is MESP2. Clinical case: Newborn male, who during the first hour of life develops perioral cyanosis, thoracoabdominal dissociation and polipnea, requiring endotracheal intubation and mechanical ventilation for respiratory impairment, finding thoracoabdominal costovertebral abnormalities with an x-ray, and a conditioning restrictive pattern like a crab. During the physical examination, we found horizontal eyelid openings, right atrial appendage, straight nasal bridge, short thorax and asymmetry and hypertrichosis, predominantly in the back. A diagnosis of dysostosis spondylothoracic is confirmed, and the patient was discharged at 7 days of age, with follow up neonatal consultation at high risk

Epidemiological Algorithm for Early Detection of COVID-19 Cases in a Mexican Oncologic Center

An early detection tool for latent COVID-19 infections in oncology staff and patients is essential to prevent outbreaks in a cancer center. (1) Background: In this study, we developed and implemented two early detection tools for the radiotherapy area to identify COVID-19 cases opportunely. (2) Methods: Staff and patients answered a questionnaire (electronic and paper surveys, respectively) with clinical and epidemiological information. The data were collected through two online survey tools: Real-Time Tracking (R-Track) and Summary of Factors (S-Facts). Cut-off values were established according to the algorithm models. SARS-CoV-2 qRT-PCR tests confirmed the positive algorithms individuals. (3) Results: Oncology staff members (n = 142) were tested, and 14% (n = 20) were positives for the R-Track algorithm; 75% (n = 15) were qRT-PCR positive. The S-Facts Algorithm identified 7.75% (n = 11) positive oncology staff members, and 81.82% (n = 9) were qRT-PCR positive. Oncology patients (n = 369) were evaluated, and 1.36% (n = 5) were positive for the Algorithm used. The five patients (100%) were confirmed by qRT-PCR. (4) Conclusions: The proposed early detection tools have proved to be a low-cost and efficient tool in a country where qRT-PCR tests and vaccines are insufficient for the population. View Full-Tex

Challenges in genetic counseling in hereditary cancer syndromes in a Mexican oncologic center

Background: In Mexico, hereditary cancer is underdiagnosed, medical geneticists give genetic counseling, but the access is limited due to the socio-economic characteristics of the population. The CUCC (Centro Universitario Contra el Cáncer) Early Cancer Detection Clinic (CECIL) created a model in which patients without cancer are enrolled in a prevention cancer screening program. Methods: From 2016 to 2021, 3014 patients were enrolled in the prevention program. Patients were evaluated with a hereditary cancer risk survey before a consultation. Those with at least one familial hereditary risk positive answer were assessed in a consultation. We also included patients with cancer diagnoses referred by oncologists of the CUCC. Those who fulfill hereditary cancer criteria were referred for genetic testing. Results: A total of 1119 subjects were evaluated. Of these, 248 (21%) were candidates for genetic testing, only 149 (60%) could be analyzed, 52 probands (59%) and 32 relatives (51%) had at least one variant. Among the probands: 33 had HBOC (Hereditary Breast and Ovarian Cancer syndrome), 7 had Lynch, 1 LFS (Li-Fraumeni syndrome), 1 LFLS (Li-Fraumeni like syndrome), 1 FAP (Familial Adenomatous Polyposis), and 9 had benign variants. In the relative\u27s group: 17 had Lynch, 10 HBOC, 1 LFS, and 4 FAP. To date, 3 patients under surveillance had an in situlesions (1 endometrial and two colon), and 3 more had a premalignant colon lesion, one in the not tested group. To achieve the genetic test cost for the probands, 50% had partial sponsors, 31% paid for their tests, research projects were supported by 13%, and 4.5% were donations. Among relatives, 94.4% paid for the tests, and 5.5% were supported by research. All relatives were tested using an in-house low-cost test. Conclusion: The model\u27s success made awareness of these diseases, leading last year to the formation of a state detection program, including all public and private health institutions attending to patients with cancer, these patients are referred to CECIL. We found an effective way to find support low-cost genetic testing via foundations

DPYD pathogenic variants associated with fluoropyrimidines toxicity

Background: Genetic variants in dihydropyrimidine dehydrogenase gene (DPYD) coding for the key enzyme (DPD) of fluoropyrimidines (FPs) catabolism. DPYD contributes to the development of severe FPs-related toxicity, and pathogenic DPYD variants detection reduces side effects and complications associated with FP-toxicity. The allelic frequency of these variants in the Mexican population is currently unknown. Methods: The study was carried out at the Centro Universitario Contra el Cáncer (CUCC) of the Universidad Autónoma de Nuevo León (UANL) in Monterrey México. Genomic DNA was isolated from 154 subjects using the QIAamp DNA Blood Midi kit (QIAGEN) following the manufacturer\u27s recommendations. We analyze the variants c.1156G-\u3eT, c.2846A-\u3eT, and c.1129-5923C-\u3eG by qPCR using predesigned probes. For the remaining genomic variants (c.1905+1G-\u3eA, c.1679T-\u3eG, c.1898delC and c.299_302delTCAT), we design sequencing oligos using the software Oligo Primer v.7®. The allele frequency was calculated for each variant. Results: We analyzed a total of 154 samples to detect the seven variants analyzed. So far, only 2 samples have been found that presented the variant c.1129-5923C\u3eG in a state of heterozygosis, representing 1.2987% of the total of our population. Conclusions: The allele frequency for the variant c.1129-5923C-\u3eG was higher than reported in other populations. So this allele is more common in our population, which could attribute to the large percentage of side effects in our patients. However, more studies and increasing the number of samples are needed to establish DPYD the allele frequency more precisely

Genotipificación de variantes germinales asociadas a síndromes de cáncer hereditario en pacientes del Noreste de México

El cáncer es un grupo de enfermedades genéticas que se caracteriza por una transformación de células normales hacia células atípicas o displasias (1). La mayoría de los casos se explica por un modelo multifactorial donde no existe una causa determinada la cual explique la etiología, sin embargo, del 5 al 10% de los casos se les conoce como síndromes de cáncer hereditario (SCH). Los pacientes con SHC tienen un riesgo incrementado de padecer neoplasias debido a que presentan variantes patogénicas germinales en genes encargados de funciones vitales de la célula como: reparación, crecimiento y diferenciación. Los SCH se expresan con un patrón de herencia mendeliano (2). Este grupo de enfermedades son evaluadas por médicos genetistas, los cuales brindan un asesoramiento genético debido a que su diagnóstico adecuado puede conllevar a cambios en el tratamiento, seguimiento y prevención de nuevas neoplasias, tanto en el paciente como en los familiares. Actualmente en nuestro país existe una deficiencia en el asesoramiento genético de estos pacientes, principalmente por la falta de personal capacitado, o por la falta de la infraestructura o programas adecuados para la evaluación y seguimiento de estos pacientes (3)

Identification of a Novel Pathogenic Rearrangement Variant of the APC Gene Associated with a Variable Spectrum of Familial Cancer

Familial adenomatous polyposis (FAP) is an autosomal-dominant condition characterized by the presence of multiple colorectal adenomas, caused by germline variants in the adenomatous polyposis coli (APC) gene. More than 300 germline variants have been characterized. The detection of novel variants is important to understand the mechanisms of pathophysiology. We identified a novel pathogenic germline variant using next-generation sequencing (NGS) in a proband patient. The variant is a complex rearrangement (c.422+1123_532-577 del ins 423-1933_423-1687 inv) that generates a complete deletion of exon 5 of the APC gene. To study the variant in other family members, we designed an endpoint PCR method followed by Sanger sequencing. The variant was identified in the proband patient’s mother, one daughter, her brother, two cousins, a niece, and a second nephew. In patients where the variant was identified, we found atypical clinical symptoms, including mandibular, ovarian, breast, pancreatic, and gastric cancer. Genetic counseling and cancer prevention strategies were provided for the family. According to the American College of Medical Genetics (ACMG) guidelines, this novel variant is considered a PVS1 variant (very strong evidence of pathogenicity), and it can be useful in association with clinical data for early surveillance and suitable treatment

Prolactin Expression in the Baboon (Papio hamadryas) Eye

Prolactin (PRL) is a hormone expressed in lactotrophs cells of the pituitary gland in primates. Extra pituitary expression of PRL has been reported, including the eye; however, expression in the developing eye of primates is limited. The aim of the study was determining the expression of PRL and PRL receptor (PRLR) (mRNAs and proteins) in adult and fetal baboon (Papio hamadryas) ocular tissues. Methods: We analyzed PRL and PRLR in baboon eyes tissues by immunofluorescence. The mRNAs of PRL and PRLR were detected by RT-PCR, cDNA was cloned, and sequenced. Furthermore, we performed a phylogenetic analysis to identify the evolutionary forces that underlie the divergence of PRL and PRLR primate genes. Results: We observed the expression of PRL and PRLR (mRNAs and proteins) in all retinal cell lineages of fetal and adult baboon. PRL and PRLR fit the hypothesis of evolutionary purifying gene selection. Conclusions: mRNA and protein of PRL and PRLR are expressed in fetal and adult baboon retinal tissue. PRL may trigger autocrine and paracrine-specific actions in retinal cell lines