Differences in Expression of IQSEC2 Transcript Isoforms in Male and Female Cases with Loss of Function Variants and Neurodevelopmental Disorder.

Pathogenic hemizygous or heterozygous mutations in the IQSEC2 gene cause X-linked intellectual developmental disorder-1 (XLID1), characterized by a variable phenotype including developmental delay, intellectual disability, epilepsy, hypotonia, autism, microcephaly and stereotypies. It affects both males and females typically through loss of function in males and haploinsufficiency in heterozygous females. Females are generally less affected than males. Two novel unrelated cases, one male and one female, with de novo IQSEC2 variants were detected by trio-based whole exome sequencing. The female case had a previously undescribed frameshift mutation (NM_001111125:c.3300dup; p.Met1101Tyrfs*5), and the male showed an intronic variant in intron 6, with a previously unknown effect (NM_001111125:c.2459+21C>T). IQSEC2 gene expression study revealed that this intronic variant created an alternative donor splicing site and an aberrant product, with the inclusion of 19bp, confirming the pathogenic effect of the intron variant. Moreover, a strong reduction in the expression of the long, but also the short IQSEC2 isoforms, was detected in the male correlating with a more severe phenotype, while the female case showed no decreased expression of the short isoform, and milder effects of the disease. This suggests that the abnormal expression levels of the different IQSEC2 transcripts could be implicated in the severity of disease manifestations.

De novo small deletion affecting transcription start site of short isoform of AUTS2 gene in a patient with syndromic neurodevelopmental defects.

Disruption of the autism susceptibility candidate 2 (AUTS2) gene through genomic rearrangements, copy number variations (CNVs), and intragenic deletions and mutations, has been recurrently involved in syndromic forms of developmental delay and intellectual disability, known as AUTS2 syndrome. The AUTS2 gene plays an important role in regulation of neuronal migration, and when altered, associates with a variable phenotype from severely to mildly affected patients. The more severe phenotypes significantly correlate with the presence of defects affecting the C-terminus part of the gene. This article reports a new patient with a syndromic neurodevelopmental disorder, who presents a deletion of 30 nucleotides in the exon 9 of the AUTS2 gene. Importantly, this deletion includes the transcription start site for the AUTS2 short transcript isoform, which has an important role in brain development. Gene expression analysis of AUTS2 full-length and short isoforms revealed that the deletion found in this patient causes a remarkable reduction in the expression level, not only of the short isoform, but also of the full AUTS2 transcripts. This report adds more evidence for the role of mutated AUTS2 short transcripts in the development of a severe phenotype in the AUTS2 syndrome.

Heterogeneous growth patterns in carriers of chromosome 7p12.2 imbalances affecting GRB10.

Chromosomal duplications and deletions in 7p12.2 have been described in patients with growth disturbance phenotypes, that is, Silver-Russell and Beckwith-Wiedemann syndrome (SRS, BWS). The region harbors the imprinted GRB10/Grb10 gene which has been postulated to belong to a major fetal growth pathway. Based on its genomic localization, its physiological function and its imprinting status, GRB10/Grb10 was considered as a candidate for growth disturbance disorders. However, based on case reports with imbalances of the GRB10 locus it has been suggested that the altered GRB10 copy number should be responsible for the aberrant growth phenotype rather than an altered imprinting status of the gene. We now report on a patient with an increased height and weight in his first years of life carrying a de-novo duplication (5.1 Mb) of paternal 7p12.2 material. The increased growth in this patient again contradicts the hypothesis that a gain of GRB10 copies leads to growth restriction. Indeed, it is necessary to compare the regions of imbalances in 7p12 and the affected genes in the different patients as other genes than GRB10 in 7p12 might cause these aberrant growth phenotypes.

Biomecánica en implantología / Biomechanics in odontology

En este artículo se realiza una valoración sobre la importancia de la biomecánica en el campo de la implantología, entendiendo a ésta, como el conjunto de fuerzas que aparecen en el proceso normal masticatorio y en las parafunciones. Nuestro estudio se centra en aquellos factores que incrementan el riesgo de que existan fuerzas nocivas y por tanto, el posible fracaso de nuestro tratamiento implantológico. En la siguiente revisión bibliográfica, hemos analizado los factores que intervienen en la aparición de una mayor fuerza de flexión, como son los oclusales, del hueso, del implante y prostodóncicos, así como aquellos que aumentan la fuerza de tracción por un mal ajuste pasivo de la prótesis implantosoportada. Finalmente explicaremos cómo diagnosticar los posibles errores biomecánicos que podrían llegar a comprometer el éxito del tratamiento (AU)

This article performs an evaluation of the importante os biomechanics within the field os implantology, understanding this as being the whole group of forces that appear within a normal masticatory process as well as in the parafunctions. Our study focuses on the factors that increase the risk that harmful forces exists, as well as the posiible failure of implantological treatment. In the folowing bibliographical revision, we had analized the factors that come into play in the appearance of greater flexion force, as are the oclusals, the bone, the implant supported prosthesis. Finally, we will explain how to disgnose possible biomechanical errors that could lead to a compromise of treatment’s success (AU)