Search results for "Nonsense"

Wilms' tumor in patients with 9q22.3 microdeletion syndrome suggests a role for PTCH1 in nephroblastomas

2012

Nephroblastoma (Wilms' tumor; WT) is the most common renal tumor of childhood. To date, several genetic abnormalities predisposing to WT have been identified in rare overgrowth syndromes. Among them, abnormal methylation of the 11p15 region, GPC3 and DIS3L2 mutations, which are responsible for Beckwith-Wiedemann, Simpson-Golabi-Behmel and Perlman syndromes, respectively. However, the underlying cause of WT remains unknown in the majority of cases. We report three unrelated patients who presented with WT in addition to a constitutional 9q22.3 microdeletion and dysmorphic/overgrowth syndrome. The size of the deletions was variable (ie, from 1.7 to 8.9 Mb) but invariably encompassed the PTCH1 …

A novel mutation of the extracellular matrix protein 1 gene (ECM1) in a patient with lipoid proteinosis (Urbach-Wiethe disease) from Sicily

2005

Summary Background  Lipoid proteinosis (LP), also known as Urbach–Wiethe disease, is a rare autosomal recessive disorder characterized by a hoarse voice, warty skin infiltration and scarring. Mutations within the extracellular matrix protein 1 (ECM1) gene cause LP. Objectives  We report the molecular analysis of the ECM1 gene in a Sicilian patient with LP in order to extend the mutation spectrum of this genodermatosis. Methods  We studied a 32-year-old female born from consanguineous parents who was diagnosed at the age of 11 years as having LP. She has a clinical phenotype corresponding to Urbach–Wiethe disease characterized by papules/nodules, indurated plaques and sometimes ulcerated les…

Identification of D179H, a novel missense GJB2 mutation in a Western Sicily family

2013

The main purpose of this study was to describe a novel missense mutation (p.D179H) found in a Western Sicily family and to examine the genetic and audiologic profiles of all family members by performing a GJB2 and GJB6 mutations analysis and a complete audiologic assessment. The proband was a 3-month-old infant with a congenital profound sensorineural hearing loss; direct sequencing of the GJB2 revealed the presence of a c.35delG mutation in the heterozygous state and a heterozygous G[C transition at nucleotide 535 in trans; this novel mutation, called p.D179H, resulted in an aspartic acid to histidine change at codon 179. It was also evidenced in the heterozygous state in two members of th…

Appearance as the Arrival of the Future

2017

AMBIGUITIES of language often indicate a problematic subject matter. That is the case with the word "appear" (erscheinen). When I say that an acquaintance (or someone with whom I was previously unacquainted) "appeared" to me, in order to speak with me, the meaning is: he came to me, he showed up in my habitat, perhaps at my home. He did not only seem (scheinen) to be there; he really was there. When something appears to us, it does not only seem to be with us, it actually is present. Appearance and existence are here very closely connected. But on the other hand, my acquaintance still exists even when he does not appear to me. Whether that would still be true if he appeared nowhere whether …

Translational readthrough of ciliopathy genes BBS2 and ALMS1 restores protein, ciliogenesis and function in patient fibroblasts

2021

Abstract Background Ciliary dysfunction underlies a range of genetic disorders collectively termed ciliopathies, for which there are no treatments available. Bardet-Biedl syndrome (BBS) is characterised by multisystemic involvement, including rod-cone dystrophy and renal abnormalities. Together with Alstrom syndrome (AS), they are known as the ‘obesity ciliopathies’ due to their common phenotype. Nonsense mutations are responsible for approximately 11% and 40% of BBS and AS cases, respectively. Translational readthrough inducing drugs (TRIDs) can restore full-length protein bypassing in-frame premature termination codons, and are a potential therapeutic approach for nonsense-mediated ciliop…

A NOVEL NONSENSE MUTATION IN THE CETP GENE IN ITALIAN HYPERALPHALIPOPROTEINEMIC SUBJECTS

2006

Functional characterisation of alpha-galactosidase a mutations as a basis for a new classification system in fabry disease.

2013

Fabry disease (FD) is an X-linked hereditary defect of glycosphingolipid storage caused by mutations in the gene encoding the lysosomal hydrolase α-galactosidase A (GLA, α-gal A). To date, over 400 mutations causing amino acid substitutions have been described. Most of these mutations are related to the classical Fabry phenotype. Generally in lysosomal storage disorders a reliable genotype/phenotype correlation is difficult to achieve, especially in FD with its X-linked mode of inheritance. In order to predict the metabolic consequence of a given mutation, we combined in vitro enzyme activity with in vivo biomarker data. Furthermore, we used the pharmacological chaperone (PC) 1-deoxygalacto…

Regulation of human inducible nitric oxide synthase expression by an upstream open reading frame.

2019

Abstract The human inducible nitric oxide synthase (iNOS) gene contains an upstream open reading frame (uORF) in its 5′-untranslated region (5′-UTR) implying a translational regulation of iNOS expression. Transfection experiments in human DLD-1 cells revealed that the uORF although translatable seems not to inhibit the translation start at the bona fide ATG. Our data clearly show that human iNOS translation is cap-dependent and that the 5′-UTR of the iNOS mRNA contains no internal ribosome entry site. Translation of the bona fide coding sequence is most likely mediated by a leaky scanning mechanism. The 5′-UTR is encoded by exon 1 and exon 2 of the iNOS gene with the uORF stop codon located…

Kinematic analysis — the sense of shear-sense. Discussion of: ‘Essay Review: Kinematic analysis — pure nonsense or simple nonsense’ by D. Flinn

1995

Enhancement of premature stop codon readthrough in the CFTR gene by Ataluren (PTC124) derivatives.

2015

Abstract Premature stop codons are the result of nonsense mutations occurring within the coding sequence of a gene. These mutations lead to the synthesis of a truncated protein and are responsible for several genetic diseases. A potential pharmacological approach to treat these diseases is to promote the translational readthrough of premature stop codons by small molecules aiming to restore the full-length protein. The compound PTC124 (Ataluren) was reported to promote the readthrough of the premature UGA stop codon, although its activity was questioned. The potential interaction of PTC124 with mutated mRNA was recently suggested by molecular dynamics (MD) studies highlighting the importanc…