Characterization of a disease-associated mutation affecting a putative splicing regulatory element in intron 6b of the cystic fibrosis transmembrane conductance regulator (CFTR) gene

Cystic fibrosis (CF) is a common recessive disorder caused by >1600 mutations in the CF transmembrane conductance regulator (CFTR) gene. About 13% of CFTR mutations are classified as “splicing mutations,” but for almost 40% of these, their role in affecting the pre-mRNA splicing of the gene is not yet defined. In this work, we describe a new splicing mutation detected in three unrelated Italian CF patients. By DNA analyses and mRNA studies, we identified the c.1002–1110_1113delTAAG mutation localized in intron 6b of the CFTR gene. At the mRNA level, this mutation creates an aberrant inclusion of a sequence of 101 nucleotides between exons 6b and 7. This sequence corresponds to a portion of intron 6b and resembles a cryptic exon because it is characterized by an upstream ag and a downstream gt sequence, which are most probably recognized as 5′- and 3′-splice sites by the spliceosome. Through functional analysis of this splicing defect, we show that this mutation abolishes the interaction of the splicing regulatory protein heterogeneous nuclear ribonucleoprotein A2/B1 with an intronic splicing regulatory element and creates a new recognition motif for the SRp75 splicing factor, causing activation of the cryptic exon. Our results show that the c.1002–1110_1113delTAAG mutation creates a new intronic splicing regulatory element in intron 6b of the CFTR gene exclusively recognized by SRp75

EL LAGO CAVIAHUE: UN AMBIENTE ÚNICO

El lago Caviahue o Agrio se sitúa en la provincia de Neuquén (dentro del departamento Ñorquinco) a 360 kilómetros de la ciudad de Neuquén, en plena cordillera de los Andes. Muy próximo al límite con Chile y a una elevación de 1.600 metros sobre el nivel del mar, el lago se encuentra además dentro del Área Protegida Provincial Copahue. Este lago neuquino se diferencia de otros cuerpos de agua de la región y del país por una serie de interesantes características que lo hacen un ambiente muy particular

3D kinematics through the X-shaped Milky Way bulge

Context. It has recently been discovered that the Galactic bulge is X-shaped, with the two southern arms of the X both crossing the lines of sight at l = 0 and | b| > 4, hence producing a double red clump in the bulge color magnitude diagram. Dynamical models predict the formation of X-shaped bulges as extreme cases of boxy-peanut bulges. However, since X-shaped bulges were known to be present only in external galaxies, models have never been compared to 3D kinematical data for individual stars. Aims. We study the orbital motion of Galactic bulge stars in the two arms (overdensities) of the X in the southern hemisphere. The goal is to provide observational constraints to bulge formation models that predict the formation of X-shapes through bar dynamical instabilities. Methods. Radial velocities have been obtained for a sample of 454 bulge giants, roughly equally distributed between the bright and the faint red clump, in a field at (l,b) = (0, −6). Proper motions were derived for all red clump stars in the same field by combining images from two epochs, which were obtained 11 years apart, with WFI at the 2.2 m at La Silla. The observed field contains the globular cluster NGC 6558, whose member stars were used to assess the accuracy of the proper motion measurement. At the same time, as a by-product, we provide the first proper motion measurement of NGC 6558. The proper motions for the spectroscopic subsample are analyzed for a subsample of 352 stars, taking into account the radial velocities and metallicities measured from near-infrared calcium triplet lines. Results. The radial velocity distribution of stars in the bright red clump, which traces the closer overdensity of bulge stars, shows an excess of stars moving towards the Sun. Similarly, an excess of stars receding from the Sun is seen in the far overdensity, which is traced by faint red clump stars. This is explained by the presence of stars on elongated orbits, which are most likely streaming along the arms of the X-shaped bulge. Proper motions for these stars are consistent with qualitative predictions of dynamical models of peanut-shaped bulges. Surprisingly, stars on elongated orbits have preferentially metal-poor (subsolar) metallicities, while the metal rich ones, in both overdensities, are preferentially found in more axisymmetric orbits. The observed proper motion of NGC 6558 has been measured as (μlcos   (b),μb) = (0.30   ±   0.14, −0.43 ± 0.13), with a velocity dispersion of (σlcos(b),σb) = (1.8,1.7) mas/yr. This is the first proper motion measurement for this cluster

A novel Fibroblast Growth Factor Receptor 2 (FGFR2) mutation associated with a mild Crouzon syndrome

[No abstract available

Evaluation of the prenatal diagnosis of limb reduction deficiencies. EUROSCAN Study Group.

Ultrasound scans in the mid-trimester of pregnancy are now a routine part of antenatal care in most European countries. Using data from registries of congenital anomalies a study was undertaken in Europe. The objective of the study was to evaluate prenatal detection of limb reduction deficiencies (LRD) by routine ultrasonographic examination of the fetus. All LRDs suspected prenatally and all LRDs (including chromosome anomalies) confirmed at birth were identified from 20 Congenital Malformation Registers from the following 12 European countries: Austria, Croatia, Denmark, France, Germany, Italy, Lithuania, Spain, Switzerland, The Netherlands, UK and Ukrainia. These registries are following the same methodology. During the study period (1996-98) there were 709,030 births, and 7,758 cases with congenital malformations including LRDs. If more than one LRD was present the case was coded as complex LRD; 250 cases of LRDs with 63 (25.2%) termination of pregnancies were identified including 138 cases with isolated LRD, 112 with associated malformations, 16 with chromosomal anomalies and 38 non chromosomal recognized syndromes. The prenatal detection rate of isolated LRD was 24.6% (34 out of 138 cases) compared with 49.1% for associated malformations (55 out of 112; p<0.01). The prenatal detection of isolated terminal transverse LRD was 22.7% (22 out of 97), 50% (3 out of 6) for proximal intercalary LRD, 8.3% (1 out of 12) for longitudinal LRD and 0 for split hand/foot; for multipli-malformed children with LRD those percentages were 46.1% (30 out of 65), 66.6% (6 out of 9), 57.1% (8 out of 14) and 0 (0 out of 2), respectively. The prenatal detection rate of LRDs varied in relation with the ultrasound screening policies from 20.0% to 64.0% in countries with at least one routine fetal scan