Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

Genetic diversity of Aedes aegypti in the central-upper Paraná Cross-Border axis in Paraguay. / Diversidad genética de aedes aegypti en el eje transfronterizo Central-Alto Paraná en Paraguay.

OBJECTIVE: To determine the genetic diversity of Aedes aegypti in the Central-Alto Paraná cross-border road corridor of Paraguay, an area that has reports of dengue cases. MATERIALS AND METHODS: Twenty adult females were selected from hatching Ae. aegypti eggs from households geolocated in the departments of Alto Paraná, Caaguazú, Cordillera and Central, between 2018 and 2019. DNA was extracted from the tissue of females for amplifying their polymorphic patterns by random amplification of polymorphic DNA by PCR (RAPD-PCR), using primers H3 and B03 in order to identify genetic parameters of population diversity. The relationships between mosquito populations according to locality were observed by unpaired arithmetic mean analysis. We used DIVA-GIS 7.3.0 and MAXENT to analyze the suitable areas of actual and potential geographic distribution of these Ae. aegypti populations. RESULTS: Forty loci were identified by RAPD-PCR profiling, with moderate gene differentiation (Gst = 0.12). The cross-border corridor presented bioclimatic conditions for the presence of variant populations of Ae. aegypti, with precipitation in the warmest quarter and mean temperature in the driest quarter being determinant in the distribution. CONCLUSIONS: There is evidence of moderate genetic diversity in Ae. aegypti populations from areas that have reported dengue cases in the cross-border road corridor linking the Central and Alto Paraná departments of Paraguay. The study of genetic variability of Ae. aegypti is very useful for entomo-epidemiological surveillance and evaluation of possible resistance to chemical control.

OBJETIVOS: Conocer la diversidad genética de Aedes aegypti en el corredor vial transfronterizo Central-Alto Paraná de Paraguay, con registros de casos de dengue. MATERIALES Y MÉTODOS: Se seleccionaron veinte hembras adultas de la eclosión de huevos de Ae. aegypti procedentes de casas geolocalizadas en los departamentos de Alto Paraná, Caaguazú, Cordillera y Central, entre el 2018 y 2019. Se extrajo ADN del tejido de las hembras para amplificación aleatoria de sus patrones polimórficos mediante amplificación aleatoria del ADN polimórfico por PCR (RAPD-PCR), usando cebadores H3 y B03 a fin de conocer parámetros genéticos de diversidad poblacional. Las relaciones entre las poblaciones de mosquitos según la localidad fueron visualizadas mediante análisis no apareado de la media aritmética. Las áreas idóneas de distribución geográfica real y potencial de estas poblaciones de Ae. aegypti fueron analizadas mediante DIVA-GIS 7.3.0 y MAXENT. RESULTADOS: Se identificaron 40 loci mediante perfiles RAPD-PCR, con diferenciación génica moderada (Gst = 0,12). El corredor transfronterizo presentó condiciones bioclimáticas para la presencia de poblaciones variantes de Ae. aegypti, siendo determinantes en la distribución la precipitación del trimestre más cálido y la temperatura media del trimestre más seco. CONCLUSIONES: Se evidencia que existe diversidad genética moderada en las poblaciones de Ae. aegypti procedentes de zonas con registros de casos de dengue ubicadas en el corredor vial transfronterizo que une los departamentos Central y Alto Paraná de Paraguay. El estudio de variabilidad genética de Ae. aegypti es de gran utilidad para la vigilancia entomoepidemiológica y evaluación de posibles eventos de resistencia al control químico.

The Proliferating Cell Nuclear Antigen (PCNA) Transcript Variants as Potential Relapse Markers in B-Cell Acute Lymphoblastic Leukemia.

Leukemia is the most common childhood malignancy in Mexico, representing more than 50% of all childhood cancers. Although treatment leads to a survival of up to 90% in developing countries, in our country, it is less than 65%. Additionally, ~30% of patients relapse with poor prognosis. Alternative splicing plays an important role in transcriptome diversity and cellular biology. This mechanism promotes an increase in the assortment of proteins with potentially distinct functions from a single gene. The proliferating cell nuclear antigen (PCNA) gene encodes two transcripts for the same protein of 261 amino acids, which is associated with several important cellular processes and with several types of cancer. However, the diversity of the transcript variants expressed in this condition is not clear. Then, we used microarray gene expression to identify changes in the exon expression level of PCNA. The data were validated using RT-PCR and Sanger sequencing, and three additional transcripts (PCNA_V3, PCNA_V4, and PCNA_V5) were identified. Computational analyses were used to determine the potential proteins resulting, their structure, and interactions with PCNA native protein and themselves. Additionally, the PCNA transcript variants were inhibited using specific siRNA, determining that their inhibition contributes to the malignant characteristics in vitro. Finally, we quantified the PCNA transcript variants in acute lymphoblastic leukemia samples and identified their expression in this disease. Based on the clinical characteristics, we determined that PCNA_V2 and PCNA_V4 are expressed at significantly low levels in relapsed B-ALL patients. We conclude that the low expression of PCNA_V2 and PCNA_V4 could be a potential molecular marker of relapse in acute lymphoblastic leukemia patients.

[Functional characterization of patients with cerebral palsy living in the Magallanes region and the Chilean Antarctic]. / Caracterización funcional de pacientes con parálisis cerebral que viven en la región de Magallanes y la Antártica Chilena.

OBJECTIVE: To functionally characterize patients with Cerebral Palsy (CP) living in the Magallanes Re gion and the Chilean Antarctic. PATIENT AND METHOD: Descriptive-retrospective observational study of patients with cerebral palsy, registered in the Outpatient Rehabilitation Program of the Corporación de Rehabilitación Club de Leones Cruz del Sur de Punta Arenas between 1986 and 2018. Patients with CP were clinically categorized and then functionally characterized according to gross motor skills (GMFCS), manual ability (MACS), feeding ability (EDACS), and communication function (CFCS). RESULTS: 106 patients were included. Regarding the clinical classification, the most common type of CP was bilateral spastic paralysis, with the highest percentage of functional involvement in each of the evaluated areas, followed by unilateral spastic paralysis, while cases of dystonic CP and other non-classifiable types presented were less frequent. According to the clinical subclassification, spastic diplegia was more frequent, especially affecting manual and communication skills level I compared with hemiplegia, while cases of mixed and unclassifiable quadriplegia were less frequent with greater overall involvement of level I feeding skills. CONCLUSION: The observed results of CP in the Magalla nes Region and the Chilean Antarctic are similar to studies available in the literature. The complete evaluation and classification of patients with CP enable a better understanding of the pathology for future studies.

Presencia de bacterias en prótesis dentales durante el proceso de elaboración / Presence of bacteria in dental prostheses during the elaboration process

Existe una creciente preocupación sobre el tema de la infección cruzada en clínicas y laboratorios dentales. El laboratorio odontológico debe seguir normas de bioseguridad que garanticen a todo el equipo de salud la prevención de estas infecciones. Los técnicos que allí laboran corren el riesgo de exponer su cara a salpicaduras, así como a rocíos de sangre y saliva. Este estudio fue diseñado para saber si los laboratorios a los que recurrimos cumplen con estas normas de bioseguridad, y qué tan confiados podemos estar de la desinfección por parte de ellos, ya que las prótesis deberían estar desinfectadas correctamente antes de colocarlas en boca (AU)

There is growing concern about the issue of cross infection in dental clinics and laboratories. The dental laboratory must follow biosafety standards that guarantee the prevention of these infections to the entire health team. The technicians who work there run the risk of exposing their face to splashes and spray of blood and saliva. This study was designed to find out if the laboratories we use comply with these biosafety standards, and how confident we can be of their disinfection by them, since the prostheses should be properly disinfected before placing them in the mouth (AU)

v-myb avian myeloblastosis viral oncogene homolog expression is a potential molecular diagnostic marker for B-cell acute lymphoblastic leukemia.

BACKGROUND: B-cell acute lymphoblastic leukemia (B-ALL) is the most commonly diagnosed childhood malignancy worldwide and is especially common in Mexico. Additionally, the number of cases has increased in recent years. Thus, it is very important to develop molecular strategies to diagnose leukemia. The aim of this study was to investigate MYB expression and to determine its impact on the diagnosis of B-ALL. METHODS: We analyzed the B-ALL gene expression profile by microarray data mining. Bioinformatics analysis was performed to identify the genes that are overexpressed in leukemia. We determined that MYB was highly expressed in leukemia. Then, we validated MYB expression in 70 patients with B-ALL and in 16 healthy controls (HCs) using qRT-PCR. The results were statistically analyzed using the Kolmogorov-Smirnov Z test, Mann-Whitney U test, receiver operating characteristic curves, and the Youden index. RESULTS: The microarrays showed that MYB was overexpressed in B-ALL patients with a fold change of 57.8728 and a P value of 2.56-195 . MYB expression showed great variability among the patients analyzed. However, compared to the HCs, the B-ALL patients had a P value < .0001, an area under the curve of 0.813, and a Youden index of 1.46, indicating the statistical significance. CONCLUSION: MYB expression in B-ALL cells could be a potential molecular marker for childhood leukemia.

Pénfigo vulgar / Pemphigus vulgaris

Resumen: El pénfigo es una enfermedad autoinmunitaria y crónica de incidencia y prevalencia bajas; sin embargo, puede alcanzar mortalidad de incluso 75% sin tratamiento. Existen dos variedades principales: el pénfigo vulgar y el foliáceo, que en términos clínicos se distinguen por la aparición de ampollas en la piel, con afección de las mucosas en los pacientes con pénfigo vulgar. En esta revisión se detalla la epidemiología, causas, fisiopatología y tratamiento de esta enfermedad, con insistencia en la importancia de los esteroides como piedra angular del tratamiento de estos pacientes.

Abstract: Pemphigus is an autoimmune and chronic disease with low incidence and preva- lence. Nevertheless it could reach a 75% mortality rate without treatment. There are two principal types: vulgar pemphigus and foliaceus pemphigus, which are clinically characterized by skin blister appearance, with mucosal affection in patients with pemphigus vulgaris. This review details the epidemiology, etiology, physiopathology and treatment of this disease, remarking the steroid importance as the cornerstone in the management of these patients.

Expression of ZNF695 Transcript Variants in Childhood B-Cell Acute Lymphoblastic Leukemia.

B-cell acute lymphoblastic leukemia is the most commonly diagnosed childhood malignancy worldwide; more than 50% of these cases are diagnosed in Mexico. Although the five-year survival rate is >80%, 30% of patients experience relapse with poor prognosis. Cancer-associated gene expression profiles have been identified in several malignancies, and some transcripts have been used to predict disease prognosis. The human transcriptome is incompletely elucidated; moreover, more than 80% of transcripts can be processed via alternative splicing (AS), which increases transcript and protein diversity. The human transcriptome is divided; coding RNA accounts for 2%, and the remaining 98% is noncoding RNA. Noncoding RNA can undergo AS, promoting the diversity of noncoding transcripts. We designed specific primers to amplify previously reported alternative transcript variants of ZNF695 and showed that six ZNF695 transcript variants are co-expressed in cancer cell lines. The amplicons were sequenced and identified. Additionally, we analyzed the expression of these six transcript variants in bone marrow from B-cell acute lymphoblastic leukemia patients and observed that ZNF695 transcript variants one and three were the predominant variants expressed in leukemia. Moreover, our results showed the co-expression of coding and long noncoding RNA. Finally, we observed that long noncoding RNA ZNF695 expression predicted survival rates.

WHOLE SEQUENCING OF THE MITOCHONDRIAL GENOME OF BREAST CANCER TISSUE IN MEXICAN-MESTIZO POSTMENOPAUSAL WOMEN WITH DIFFERENT BODY MASS INDEX.

BACKGROUND: Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. OBJECTIVE: The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). SUBJECTS AND METHODS: We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients' genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. RESULTS: Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. CONCLUSIONS: We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.

Whole sequencing of the mitochondrial genome of breast cancer tissue in Mexican-mestizo postmenopausal women with different body mass index

Abstract Background Mitochondrial and oxidative stress has been related to obesity and breast cancer being this cancer more frequent and more aggressive in postmenopausal women with obesity. Objective The objective of this study was to investigate whether Mexican-Mestizo postmenopausal women with breast cancer and obesity present different somatic mutations in the mitochondrial DNA (mtDNA) when compared to women with normal body mass index (BMI). Subjects and Methods We included six Mexican-Mestizo postmenopausal women bearing breast cancer and who underwent mastectomy or breast-conserving surgery. BMI was determined in each case. Patients’ genomic DNA was isolated from blood leukocytes and tumor tissue samples. Whole mtDNA sequence was determined by MitoChip v2.0 mitochondrial resequencing array, and data were analyzed using the GeneChip Sequence Analysis Software. Tumor mtDNA sequence was compared with matched leukocyte mtDNA sequence. Results Three women had a normal BMI and three presented obesity. Overall, we found 64 genetic variants: 53.1% were somatic mutations and 46.9% were polymorphisms; 44.1% were in the non-coding region and 55.9% were in genes that encode for mitochondrial proteins. Among the somatic mutations, 67.7% were in patients with normal BMI and 32.3% in patients with obesity. Conclusions We did not find a higher frequency of mitochondrial somatic mutations in postmenopausal women with breast cancer and obesity compared to those with normal BMI. However, results could be due to the small number of women studied.

Identification and Validation of Novel Reference Genes in Acute Lymphoblastic Leukemia for Droplet Digital PCR.

Droplet digital PCR is the most robust method for absolute nucleic acid quantification. However, RNA is a very versatile molecule and its abundance is tissue-dependent. RNA quantification is dependent on a reference control to estimate the abundance. Additionally, in cancer, many cellular processes are deregulated which consequently affects the gene expression profiles. In this work, we performed microarray data mining of different childhood cancers and healthy controls. We selected four genes that showed no gene expression variations (PSMB6, PGGT1B, UBQLN2 and UQCR2) and four classical reference genes (ACTB, GAPDH, RPL4 and RPS18). Gene expression was validated in 40 acute lymphoblastic leukemia samples by means of droplet digital PCR. We observed that PSMB6, PGGT1B, UBQLN2 and UQCR2 were expressed ~100 times less than ACTB, GAPDH, RPL4 and RPS18. However, we observed excellent correlations among the new reference genes (p < 0.0001). We propose that PSMB6, PGGT1B, UBQLN2 and UQCR2 are housekeeping genes with low expression in childhood cancer.

Centromere-associated protein E expresses a novel mRNA isoform in acute lymphoblastic leukemia.

The alternative splicing plays an important role to generate protein diversity. Recent studies have shown alterations in alternative splicing, resulting in loss, gain or changes of functions in the resulting protein. Specific products of alternative splicing are known to contribute in cancer-related mechanisms, such as angiogenesis, migration, adhesion and cell proliferation, among others. We using high-density microarrays reported a CENP-E as a one of significant transcript expressed and potentially is alternatively spliced in cancer. We focus in validate alternative splicing of CENP-E transcript using RT-PCR and sequencing in different cancer cell lines. We performed RT-PCR using specific primers designed to delimit the non-reported alternative splicing in CENP-E transcript. Our results showed the co-expression of the variant one and two of CENP-E in all cell lines evaluated. We detected more expression of variant one than two. Moreover, we identify an alternative 5'splice site of CENP-E in the exon 38 and was observed in RoVa cell line. Additionally, we characterized alternative skipping from exon 20 (NAT-CENP-E), these alternative splicing was observed in all cell lines evaluated except RoVa. Finally, we corroborate alternative mRNA splicing in leukemia patients using quantitative RT-PCR, in 71.8% of the patients NAT-CENP-E is downregulated and 28.2% is overexpressed.

Genome-wide mRNA analysis reveals a TUBD1 isoform profile as a potential biomarker for diabetic retinopathy development.

Diabetic retinopathy (DR) affects approximately one third of all diabetic subjects and is the leading cause of blindness in young to middle-aged adults in the developed world. While early diagnosis is crucial for preventing DR-associated visual loss, the identification of accessible biomarkers that could lead to presymptomatic recognition of the disease is of great clinical importance. The aim of this work was to investigate the possible involvement of alternative splicing events in DR development by performing a genome-wide transcriptional profiling comparing blood-derived RNA from DR subjects and from diabetic-non DR controls. A total of 95 RNA samples, 67 from patients with bilateral DR and 28 from diabetic patients without DR after a period of at least 10 years with type 2 DM, were compared in a genome-wide transcriptome analysis using the GeneChip® Human Gene 2.0 ST Array which contains probe sets covering all exons of ∼33,500 coding transcripts of annotated genes. Microarray data analysis followed by RT-PCR and cDNA sequencing identified important differential splicing events in TUBD1 (Tubulin, Delta-1) isoforms between DR and DM samples. Specifically, the co-expression of particular TUBD1 isoforms was significantly associated with NPDR risk (p = 0.039 by Pearson's chi-squared test; OR (CI 95%): 8.1 (1.0-72.7)). Analysis of TUBD1 signal pathways and regulating networks using a MetaCore platform showed that HIF-1, a molecule playing an important role in the pathogenesis of DR, is a direct regulator of TUBD1 expression. In conjunction, our data suggest that TUBD1 mRNA isoform expression profile in peripheral blood could be an accessible biomarker for predicting the risk for diabetic retinopathy development.

Exome sequencing identifies a de novo frameshift mutation in the imprinted gene ZDBF2 in a sporadic patient with Nasopalpebral Lipoma-coloboma syndrome.

Nasopalpebral lipoma-coloboma syndrome (NPLCS, OMIM%167730) is an uncommon malformation entity with autosomal dominant inheritance characterized by the combination of nasopalpebral lipoma, colobomas in upper and lower eyelids, telecanthus, and maxillary hypoplasia. To date, no genetic defects have been associated with familial or sporadic NPLCS cases and the etiology of the disease remains unknown. In this work, the results of whole exome sequencing in a sporadic NPLCS patient are presented. Exome sequencing identified a de novo heterozygous frameshift dinucleotide insertion c.6245_6246 insTT (p.His2082fs*67) in ZDBF2 (zinc finger, DBF-type containing 2), a gene located at 2q33.3. This variant was absent in parental DNA, in a set of 300 ethnically matched controls, and in public exome variant databases. This is the first genetic variant identified in a NPLCS patient and evidence supporting the pathogenicity of the identified mutation is discussed. © 2016 Wiley Periodicals, Inc.

Characterization and mRNA expression analysis of a novel ARG1 splicing mutation causing hyperargininemia.

OBJECTIVES: Biallelic mutations in the ARG1 gene result in an uncommon autosomal recessive inborn defect of the urea cycle known as hyperargininemia (OMIM #207800). ARG1 splicing mutations are not reported often, and they are probably related to a more severe phenotype than missense mutations. In this article, we describe the results of molecular studies in a young hyperargininemia patient carrying a novel splicing mutation in ARG1. DESIGN AND METHODS: Molecular analyses included PCR amplification and direct nucleotide sequencing of the ARG1 gene. RT-PCR analysis was performed to investigate the effect of the mutation in mRNA splicing and in the expression of ARG1 isoforms. RESULTS: Mutational analysis identified a novel homozygous ARG1 IVS4-1G>C point mutation in the patient's DNA. Blood leukocyte mRNA was analyzed to demonstrate the splicing defect caused by this mutation. Sequencing of ARG1 RT-PCR products allowed the characterization of a mutated transcript retaining 51-bp from intron 4. In addition, two new, alternatively spliced ARG1 transcripts lacking either exon 4 or exons 4 and 5 were identified in mRNA from the patient and from controls. CONCLUSIONS: Our results expand the mutational spectrum in hyperargininemia patients and indicate that the novel splicing mutation results in an aberrant transcript retaining intronic sequences. Two novel alternatively spliced ARG1 transcripts were also recognized.

Acro-spondylo-pubic dysostosis associated with cataracts, microcephaly, and normal intelligence.

We report on an adult male with normal intelligence who exhibited an unusual combination of microcephaly, dysostoses of limbs, vertebrae, patellae, and pubic bone, camptodactyly of all fingers, and syndactyly of toes, absent nails on thumbs and some fingers, bilateral cataract, cryptorchidism, polythelia, and nipple-like skin pigmentations of shoulders and upper back. We have been unable to find a description of a similar combination of manifestations in literature. The cause of the anomalies remains unknown.

Heterogeneity of microRNAs expression in cervical cancer cells: over-expression of miR-196a.

In recent years, the study of microRNAs associated with neoplastic processes has increased. Patterns of microRNA expression in different cell lines and different kinds of tumors have been identified; however, little is known about the alterations in regulatory pathways and genes involved in aberrant set of microRNAs. The identification of these altered microRNAs in several cervical cancer cells and potentially deregulated pathways involved constitute the principal goals of the present study. In the present work, the expression profiles of cellular microRNAs in Cervical Cancer tissues and cell lines were explored using microRNA microarray, Affymetrix. The most over-expressed was miR-196a, which was evaluated by real time PCR, and HOXC8 protein as potential target by immunohistochemistry assay. One hundred and twenty three human microRNAs differentially expressed in the cell tumor, 64 (52%) over-expressed and 59 (48%) under-expressed were observed. Among the microRNAs over-expressed, we focused on miR-196a; at present this microRNA is poorly studied in CC. The expression of this microRNA was evaluated by qRT-PCR, and HOXC8 by immunohistochemistry assay. There is not a specific microRNA expression profile in the CC cells, neither a microRNA related to HPV presence. Furthermore, the miR-196a was over-expressed, while an absence of HOXC8 expression was observed. We suggest that miR-196a could be played as oncomiR in CC.

Identification and expression analysis of a novel intragenic EFNB1 mutation causing craniofrontonasal syndrome.

Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by mutations in the EFNB1 gene and characterized by distinctive craniofacial and digital malformations. In contrast with most X-linked traits, female patients with CFNS display a more severe phenotype than males. In this report, the clinical, molecular and RNA expression analyses of a female subject with CFNS are described. A novel c.445_449delGAGGG deletion in exon 3 of EFNB1 was demonstrated in this patient. To assess the effect of this novel mutation at the transcript level, the expression of EFNB1 mRNA was studied by quantitative RT-PCR. To our knowledge, this is the first time that an EFNB1 transcript carrying a truncating mutation in exon 3 is demonstrated to undergo degradation by nonsense-mediated mRNA decay. Our results expand the mutational spectrum of CFNS and add to the functional consequences of truncating EFNB1 mutations.

Splice variants of zinc finger protein 695 mRNA associated to ovarian cancer.

BACKGROUND: Studies of alternative mRNA splicing (AS) in health and disease have yet to yield the complete picture of protein diversity and its role in physiology and pathology. Some forms of cancer appear to be associated to certain alternative mRNA splice variants, but their role in the cancer development and outcome is unclear. METHODS: We examined AS profiles by means of whole genome exon expression microarrays (Affymetrix GeneChip 1.0) in ovarian tumors and ovarian cancer-derived cell lines, compared to healthy ovarian tissue. Alternatively spliced genes expressed predominantly in ovarian tumors and cell lines were confirmed by RT-PCR. RESULTS: Among several significantly overexpressed AS genes in malignant ovarian tumors and ovarian cancer cell lines, the most significant one was that of the zinc finger protein ZNF695, with two previously unknown mRNA splice variants identified in ovarian tumors and cell lines. The identity of ZNF695 AS variants was confirmed by cloning and sequencing of the amplicons obtained from ovarian cancer tissue and cell lines. CONCLUSIONS: Alternative ZNF695 mRNA splicing could be a marker of ovarian cancer with possible implications on its pathogenesis.

Prevalence of human papillomavirus in the cervical epithelium of Mexican women: meta-analysis.

BACKGROUND: Human Papillomavirus (HPV) in cervical epithelium has been identified as the main etiological factor in the developing of Cervical Cancer (CC), which has recently become a public health problem in Mexico. This finding has allowed for the development of vaccines that help prevent this infection. In the present study, we aimed to determine the prevalence and HPV type-distribution in Mexican women with CC, high-grade squamous intraepithelial lesion (HSIL), low-grade squamous intraepithelial lesion (LSIL), and Normal cytology (N) to estimate the impact of the HPV vaccines. METHODS: The PubMed database was used to identify and review all articles that reported data on HPV prevalence in CC, precursor lesions, and normal cytology of Mexican women. RESULTS: A total of 8,706 samples of the tissues of Mexican women were stratified according to diagnosis as follows: 499 for CC; 364 for HSIL; 1,425 for LSIL, and 6,418 for N. According to the results, the most prevalent genotypes are the following: HPV16 (63.1%), -18 (8.6%), -58, and -31 (5%) for CC; HPV-16 (28.3%), 58 (12.6%), 18 (7.4%), and 33 (6.5%) for HSIL; HPV-16 (13.1%), 33 (7.4%), 18 (4.2%), and 58 (2.6%) for LSIL, and HPV-16 (3.4%), 33 (2.1%), 18, and 58 (1.2%) for N. CONCLUSIONS: Taken together, genotypes 58 and 31 (10%) are more common than type 18 (8.6%) in CC. Therefore, the inclusion of these two genotypes in a second-generation vaccine would provide optimal prevention of CC in Mexico.