Search results for "missense"

Copy number variation and missense mutations in the caprine agouti signaling protein (ASIP) gene are present in goat breeds with different coat colour

2008

GENETIC NEUROCHAPERONOPATHIES ASSOCIATED WITH CCT5 AND HSP60 VARIANTS: ANALYSIS OF THEIR MOLECULAR ANATOMY AND POSSIBLE PATHOGENIC IMPLICATIONS

2022

FUNCTIONAL CHARACTERIZATION OF NOVEL AMINO ACID VARIANTS IN APOB IN FAMILIAL HYPOBETALIPOPROTEINEMIA

2013

Introduction. Familial Hypobetalipoproteinemia (FHBL) is a codominant disorder characterized by reduced levels of LDL and apolipoprotein B (apoB) in plasma. In approximately 50% of FHBL cases is due to mutations in APOB gene resulting in truncated apoBs of various size. Only a few missense mutations have been reported so far as the cause of FHBL. In vitro studies have shown that these mutations induce retention of the mutant apoB in the endoplasmic reticulum and impair the secretion of apoB-containing lipoproteins. We identi ed two novel amino acid variants (Thr26-27del and Tyr102Cys) located in the N-terminal 1000 amino acids of mature apoB in two hypocholesterolemic blood donors. Methods.…

Missense and nonsense mutations in melanocortin 1 receptor (MC1R) gene of different goat breeds: association with red and black coat colour phenotype…

2009

Abstract Background Agouti and Extension loci control the relative amount of eumelanin and pheomelanin production in melanocytes that, in turn, affects pigmentation of skin and hair. The Extension locus encodes the melanocortin 1 receptor (MC1R) whose permanent activation, caused by functional mutations, results in black coat colour, whereas other inactivating mutations cause red coat colour in different mammals. Results The whole coding region of the MC1R gene was sequenced in goats of six different breeds showing different coat colours (Girgentana, white cream with usually small red spots in the face; Maltese, white with black cheeks and ears; Derivata di Siria, solid red; Murciano-Granad…

The Molecular Basis of X-Linked Spondyloepiphyseal Dysplasia Tarda

2001

The X-linked form of spondyloepiphyseal dysplasia tarda (SEDL), a radiologically distinct skeletal dysplasia affecting the vertebrae and epiphyses, is caused by mutations in the SEDL gene. To characterize the molecular basis for SEDL, we have identified the spectrum of SEDL mutations in 30 of 36 unrelated cases of X-linked SEDL ascertained from different ethnic populations. Twenty-one different disease-associated mutations now have been identified throughout the SEDL gene. These include nonsense mutations in exons 4 and 5, missense mutations in exons 4 and 6, small (2–7 bp) and large (>1 kb) deletions, insertions, and putative splicing errors, with one splicing error due to a complex deleti…

A novel S379A TARDBP mutation associated to late-onset sporadic ALS

2019

Since 2008, several groups have reported a lot of dominant mutations in TARDBP gene as a primary cause of Amyotrophic lateral sclerosis (ALS). Mutations in TARDBP gene are responsible for 4–5% of familial ALS (fALS) and nearly 1% of sporadic ALS (sALS). To date, over 50 dominant mutations were found in TDP-43 in both familial and sporadic ALS patients, most of which were missense mutations in the C-terminal glycine-rich region. Herein, we describe the clinical and genetic analysis of an Italian non-familial ALS patient with a late onset and a rapid disease progression, which led to the discovery of a novel TARDBP mutation. After neurological evaluation, molecular investigation highlighted t…

Phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathy.

2014

Objective: To clarify the phenotypic spectrum and incidence of TRPV4 mutations in patients with inherited axonal neuropathies. Methods: We screened for TRPV4 mutations in 169 French unrelated patients with inherited axonal peripheral neuropathy. Ninety-five patients had dominant Charcot-Marie-Tooth type 2 (CMT2) disease, and 74 patients, including 39 patients with distal hereditary motor neuropathy, 14 with congenital spinal muscular atrophy and arthrogryposis, 13 with CMT2, and 8 with scapuloperoneal spinal muscular atrophy, presented with additional vocal cord paralysis and/or skeletal dysplasia. Results: No deleterious TRPV4 mutation was identified in the 95 patients with “pure” CMT2 (0/…

Structure-based engineering of strictosidine synthase: auxiliary for alkaloid libraries.

2007

SummaryThe highly substrate-specific strictosidine synthase (EC 4.3.3.2) catalyzes the biological Pictet-Spengler condensation between tryptamine and secologanin, leading to the synthesis of about 2000 monoterpenoid indole alkaloids in higher plants. The crystal structure of Rauvolfia serpentina strictosidine synthase (STR1) in complex with strictosidine has been elucidated here, allowing the rational site-directed mutation of the active center of STR1 and resulting in modulation of its substrate acceptance. Here, we report on the rational redesign of STR1 by generation of a Val208Ala mutant, further describing the influence on substrate acceptance and the enzyme-catalyzed synthesis of 10-m…

Analysis of the p53 and MDM-2 gene in acute myeloid leukemia

1996

The MDM-2 (murine double minute 2) gene codes for a cellular protein that can bind to the p53 tumor suppressor gene product, thereby functioning as a negative regulator of p53. In order to define the role of the MDM-2 gene in the pathogenesis of human acute myeloid leukemia, the expression and the sequence of the MDM-2 gene were examined in samples of bone marrow and/or peripheral mononuclear cells of 38 patients by using immunostaining, polymerase chain reaction (PCR), single strand conformation polymorphism, and sequencing. Immunohistochemical staining detected a weak accumulation of the MDM-2 protein in AML patients of FAB classification M4 and M5. RT-PCR analysis revealed a heterogeneou…

A029 Identification of polymorphisms in the gene encoding secreted phospholipase A2 group X and study of their role in coronary artery disease. The a…

2009

Human secreted phospholipases A2 (sPLA2s) represent novel attractive therapeutic targets and biomarkers in coronary artery diseases (CAD). We have shown that human Group X sPLA2 (hGX sPLA2) is present in atherosclerotic lesions and that hGX sPLA2 modified LDL induces foam cell formation. To elucidate whether hGX sPLA2 has a causative role in CAD we have screened the human PLA2G10 gene to identify frequent polymorphisms, and we have examined their possible association with cardiovascular end-points and intermediate inflammatory phenotypes in a large prospective study of patients with CAD (the AtheroGene study). Although no significant association was found between the various polymorphisms i…