Análisis petrográfico de rocas de composición máfica en la serranía de Carpintero (Alta Guajira)

La península de la Guajira registra una historia compleja debido a procesos de tectónica que se han producido en la región dando origen a varias unidades litológicas. En este trabajo se realizó descripción petrográfica y las texturas de deformación de las rocas de composición máfica en la Serranía de Carpintero. Se encontraron en los cuerpos de peridotitas microestructuras de tipo dominó, estructuras SC, texturas de malla y de tipo reloj de arena. Estas rocas comprendían una estructura mineral de ~40% clinopiroxenos, ~30% ortopiroxenos, ~35% talco, ~30% serpentina, ~10% clorita y ~20% minerales opacos en su mayoría. Las muestras de basalto exhibían una mineralogía que constaba de ~45% tremolita, ~30% epidota, ~20% plagioclasas, ~25% venas de calcita acompañada de una foliación marcada por lo que se clasificó la roca como metabasalto. Del mapa y el corte regional se pudo interpretar que la secuencia de rocas máficas se encuentra cabalgando sobre las rocas meta sedimentarias. Esto, debido al emplazamiento de la ofiolita relacionado al borde colisional entre el arco intraoceánico y el margen noroccidental suramericano en el Cretácico Tardío, el cual se ve reflejado en evidencias como desplazamiento sinestral hacia 124 (SE) identificado en una peridotita cizallada. Y por último se estableció una correlación pseudoestratigrafica entre la Fm Carpintero, Fm Etpana y Fm Jarara.PregradoGeólog

Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs

Genetic testing of the cystic fibrosis transmembrane conductance ( CFTR) gene is currently performed in couples undergoing assisted reproduction techniques ( ART), because of the high prevalence of healthy carriers in the population and the pathogenic relationship with congenital bilateral absence of vas deferens ( CBAVD). However, discordant data have been reported concerning the usefulness of this genetic test in couples with no family history of cystic fibrosis ( CF). In this study, we report the results of CFTR molecular screening in 1195 couples entering ART. Genetic testing was initially carried out in a single partner of each couple. CFTR mutations were detected in 55 subjects ( 4.6%), a percentage that overlaps with the one reported in the general population. However, significantly higher frequencies of were found in CBAVD individuals ( 37.5%) and in males with nonobstructive azoospermia ( 6.6%). The 5T allele was found in 78 patients ( 6.5%). This figure was again significantly different in males with nonobstructive-azoospermia ( 9.9%) and in those with CBAVD ( 100%). All together, 139 subjects ( 11.6%) had either a CFTR mutation or the 5T allele. Subsequent molecular analysis of their partners disclosed a CFTR mutation or 5T allele in nine cases ( 6.5%). However, none of these couples had CFTR alterations in both members, a CFTR mutation being invariably present in one partner and the 5T allele in the other. In order to improve genetic counselling of these couples, the TG-M470V-5T association was analyzed, and a statistically significant relationship between 12TG-V470 and CBAVD was detected

Functional analysis of splicing mutations in exon 7 of NF1 gene

BACKGROUND: Neurofibromatosis type 1 is one of the most common autosomal dominant disorders, affecting about 1:3,500 individuals. NF1 exon 7 displays weakly defined exon-intron boundaries, and is particularly prone to missplicing. METHODS: In this study we investigated the expression of exon 7 transcripts using bioinformatic identification of splicing regulatory sequences, and functional minigene analysis of four sequence changes [c.910C>T (R304X), c.945G>A/c.946C>A (Q315Q/L316M), c.1005T>C (N335N)] identified in exon 7 of three different NF1 patients. RESULTS: Our results detected the presence of three exonic splicing enhancers (ESEs) and one putative exonic splicing silencer (ESS) element. The wild type minigene assay resulted in three alternative isoforms, including a transcript lacking NF1 exon 7 (NF1ΔE7). Both the wild type and the mutated constructs shared NF1ΔE7 in addition to the complete messenger, but displayed a different ratio between the two transcripts. In the presence of R304X and Q315Q/L316M mutations, the relative proportion between the different isoforms is shifted toward the expression of NF1ΔE7, while in the presence of N335N variant, the NF1ΔE7 expression is abolished. CONCLUSION: In conclusion, it appears mandatory to investigate the role of each nucleotide change within the NF1 coding sequence, since a significant proportion of NF1 exon 7 mutations affects pre-mRNA splicing, by disrupting exonic splicing motifs and modifying the delicate balance between aberrantly and correctly spliced transcripts

Biallelic mutations in DYNC2LI1 are a rare cause of Ellis-van Creveld syndrome

Ellis van Creveld syndrome (EvC) is a chondral and ectodermal dysplasia caused by biallelic mutations in the EVC, EVC2 and WDR35 genes. A proportion of cases with clinical diagnosis of EvC, however, do not carry mutations in these genes. To identify the genetic cause of EvC in a cohort of mutation-negative patients, exome sequencing was undertaken in a family with three affected members, and mutation scanning of a panel of clinically and functionally relevant genes was performed in 24 additional subjects with features fitting/overlapping EvC. Compound heterozygosity for the c.2T>C (p.Met1?) and c.662C>T (p.Thr221Ile) variants in DYNC2LI1, which encodes a component of the intraflagellar transport-related dynein-2 complex previously found mutated in other short-rib thoracic dysplasias, was identified in the three affected members of the first family. Targeted resequencing detected compound heterozygosity for the same missense variant and a frameshift change (p.Val141*) in two siblings with EvC from a second family, while a newborn with a more severe phenotype carried two DYNC2LI1 truncating variants. Our findings indicate that DYNC2LI1 mutations are associated with a wider clinical spectrum than previously appreciated, including EvC, with the severity of the phenotype likely depending on the extent of defective DYNC2LI1 function

Identification of the second CFTR mutation in patients with congenital bilateral absence of vas deferens undergoing ART protocols.

Congenital bilateral absence of vas deferens (CBAVD) is a manifestation of the mildest form of cystic fibrosis (CF) and is characterized by obstructive azoospermia in otherwise healthy patients. Owing to the availability of assisted reproductive technology, CBAVD patients can father children. These fathers are at risk of transmitting a mutated allele of the CF transmembrane conductance regulator (CFTR) gene, responsible for CF, to their offspring. The identification of mutations in both CFTR alleles in CBAVD patients is a crucial requirement for calculating the risk of producing a child with full-blown CF if the female partner is a healthy CF carrier. However, in the majority of CBAVD patients, conventional mutation screening is not able to detect mutations in both CFTR alleles, and this difficulty hampers the execution of correct genetic counselling. To obtain information about the most represented CFTR mutations in CBAVD patients, we analysed 23 CBAVD patients, 15 of whom had a single CFTR mutation after screening for 36 mutations and the 5T allele. The search for the second CFTR mutation in these cases was performed by using a triplex approach: (i) first, a reverse dot-blot analysis was performed to detect mutations with regional impact; (ii) next, multiple ligation-dependent probe amplification assays were conducted to search for large rearrangements; and (iii) finally, denaturing high-performance liquid chromatography was used to search for point mutations in the entire coding region. Using these approaches, the second CFTR mutation was detected in six patients, which increased the final detection rate to 60.8%

Four-year follow-up study in a NF1 Boy with a focal pontine hamartoma

Abstract Neurofibromatosis is a collective name for a group of genetic conditions in which benign tumours affect the nervous system. Type 1 is caused by a genetic mutation in the NF1 gene (OMIM 613113) and symptoms can vary dramatically between individuals, even within the same family. Some people have very mild skin changes, whereas others suffer severe medical complications. The condition usually appears in childhood and is diagnosed if two of the following are present: six or more café-au-lait patches larger than 1.5 cm in diameter, axillary or groin freckling, 2 or more Lisch nodules (small pigmented areas in the iris of the eye), 2 or more neurofibromas, optic pathway gliomas, bone dysplasia, and a first-degree family relative with Neurofibromatosis type 1. The pattern of inheritance is autosomal dominant, however, half of all NF1 cases are ‘sporadic’ and there is no family history. Neurofibromatosis type 1 is an extremely variable condition whose morbidity and mortality is largely dictated by the occurrence of the many complications that may involve any of the body systems. We describe a family affected by NF1 in whom genetic molecular analysis identified the same mutation in the son and father. Routine MRI showed pontine focal lesions in the eight-year-old son, though not in the father. We performed a four years follow-up study and at follow-up pontine hamartoma size remained unchanged in the son, and the father showed still no brain lesions, confirming thus an intra-familial phenotype variability.</p

Germline mosaicism in neurofibromatosis type 1 due to a paternally derived multi-exon deletion

We report on the clinical and molecular features of a family in which neurofibromatosis type 1 (NF1) occurred in two of three siblings born to unaffected parents and in one granddaughter. Linkage analysis showed that the two affected siblings and the daughter of one of them shared the same paternal allele, whereas they had inherited different maternal alleles. We detected a disease-causing deletion (c.4773-3622-?_5749+?del) encompassing three NF1 gene exons in affected individuals. This mutation occurred on the paternally derived allele, arguing for a germline mosaicism in the probands' father. Real-time PCR showed that the mutation was present in about 10-17% of the paternal sperms. Current results confirm that germline mosaicism can explain the recurrence of NF1 in offspring of unaffected parents. (C) 2010 Wiley-Liss, Inc

Bilateral (opercular and paracentral lobular) polymicrogyria and neurofibromatosis type 1

Anecdotal cases of polymicrogyria (PMG; a malformation of cortical development consisting of an excessive number of small gyri with abnormal lamination) in patients with neurofibromatosis type 1 (NF1) have been described; however, the cases were unilateral and had negative NF1 genetic testing. We describe an 11-year-old girl with NF1 manifesting as a complex epileptic syndrome, including partial seizures secondarily generalized and status epilepticus, who had in association, bilateral, asymmetrical (opercular and paracentral lobular) PMG. She had a 1-bp deletion (c.1862delC) in exon 12b of the NF1 gene. It is notable that, given the key role played by the NF1 gene product, neurofibromin, in normal brain development, and the relatively high frequency of other brain findings in NF1, there are not more NF1 cases with brain malformations manifesting as PMG. © 2011 Wiley-Liss, Inc