Search results for "mutation."
showing 10 items of 2808 documents
Thrombosis in inherited factor VII deficiency
2003
Thrombosis in congenital factor (F) VII deficiency was investigated through extensive phenotypic and molecular-genetic studies. Patients with a history of thrombosis among 514 entries in the FVII Deficiency Study Group database were evaluated. Thrombotic events were arterial in one case, disseminated intravascular coagulation in another and venous in seven. Gene mutations were characterized in eight patients: three were homozygous, three compound heterozygous and two heterozygous. FXa and IIa generation assays were consistent with the genetic lesions. One patient was heterozygous for the FV Leiden and one for the FIIG20210A mutation. In seven patients, surgical interventions and/or replacem…
Genetic Variation at the ApoA-IV Gene Locus and Response to Diet in Familial Hypercholesterolemia
1998
Abstract —Plasma lipid response to dietary fat and cholesterol is, in part, genetically controlled. The apolipoprotein A-IV (apoA-IV protein; APOA4, gene) has been shown to influence the response to dietary changes in normolipidemic individuals. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, and no studies are available on the influence of APOA4 mutations on dietary response in these subjects. We studied the effect of 2 common apoA-IV genetic variants (Gln 360 →His and Thr 347 →Ser) on the lipid response to the National Cholesterol Education Program type I (NCEP-I) diet in 67 FH heterozygotes (43 women and 24 men). Subjects were studied at baseli…
Evaluation of the autoimmune regulator (AIRE) gene mutations in a cohort of Italian patients with autoimmune-polyendocrinopathy-candidiasis-ectoderma…
2009
Summary Objective Autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is a rare syndrome characterized by chronic candidiasis, chronic hypoparathyroidism and Addison's disease. APECED has been associated with mutations in autoimmune regulator (AIRE) gene. Our aim is to perform a genetic analysis of the AIRE gene in Italian APECED patients and in their relatives. Design AIRE mutations were determined by DNA sequencing in all subjects. Patients were tested for clinical autoimmune or non-autoimmune diseases, or for organ and non-organ specific autoantibodies. Patients A total of 24 Italian patients with APECED (15 from the Venetian region, 2 from Southern-Tyrol, 4 from…
Mutation screening for the prothrombin variant G20210A by melting point analysis with the Light Cycler system: atypical results, detection of the var…
2005
In the differential diagnosis of thrombophilic disorders genotyping of prothrombin and factor V are nowadays performed as a routine analysis. In the following we describe the unusual results of the mutation screening using melting point analysis for two patients and the consecutive detection of the mutation C20209T by sequencing the corresponding gene fragments. The molecular result is discussed with special respect to the medical history, ethnic background and clinical findings of both patients.
Molecular basis of a new type of C1q-deficiency associated with a non-functional low molecular weight (LMW) C1q: parallels and differences to other k…
1998
Analysis of an abnormal C1q molecule of individuals of a Moroccan family by ultracentrifugation in sucrose gradients revealed a low molecular weight C1q (LMW-C1q). We investigated the molecular basis of this defect by sequencing all six exons of the three C1q genes. One point mutation in the codon for Gly at position 15 (GGT) of the B chain was found resulting in an amino acid substitution to Asp (GAT). The exchange not only leads to an interruption of the collagen-like motif Gly-X-Y, but also introduces one negatively charged residue per B chain which results in two additional charges per structural subunit (A-B, C-C, A-B). The mutation which has been identified by DNA-sequencing in the C1…
KIAA0556 is a novel ciliary basal body component mutated in Joubert syndrome
2015
Background Joubert syndrome (JBTS) and related disorders are defined by cerebellar malformation (molar tooth sign), together with neurological symptoms of variable expressivity. The ciliary basis of Joubert syndrome related disorders frequently extends the phenotype to tissues such as the eye, kidney, skeleton and craniofacial structures. Results Using autozygome and exome analyses, we identified a null mutation in KIAA0556 in a multiplex consanguineous family with hallmark features of mild Joubert syndrome. Patient-derived fibroblasts displayed reduced ciliogenesis potential and abnormally elongated cilia. Investigation of disease pathophysiology revealed that Kiaa0556-/- null mice possess…
Impact of HBV genotypes A and D genetic variability on infection evolution
2015
HBV is characterized by a high genetic variability, which is the basis of its classification into eight genotypes (A-H). HBV infection is associated with different outcomes, from self-limiting acute hepatitis to active chronic hepatitis, asymptomatic carriage, and occult infection. The aim of this study was to analyze the genetic variability of HBV genotypes A and D isolates from 79 cases of self-limiting acute hepatitis and chronic hepatitis, in order to identify HBV variants associated with resolution or chronicity of acute HBV infection. The entire preS-S sequence and a fragment of 346 bp of the preC-C region, containing Enhancer II and Basal Core Promoter sequences, were analyzed. A phy…
Ten new cases further delineate the syndromic intellectual disability phenotype caused by mutations in DYRK1A.
2015
The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specificall…
A two base pair deletion in the PQBP1 gene is associated with microphthalmia, microcephaly, and mental retardation.
2007
X-linked mental retardation has been traditionally divided into syndromic (S-XLMR) and non-syndromic forms (NS-XLMR), although the borderlines between these phenotypes begin to vanish and mutations in a single gene, for example PQBP1, can cause S-XLMR as well as NS-XLMR. Here, we report two maternal cousins with an apparently X-linked phenotype of mental retardation (MR), microphthalmia, choroid coloboma, microcephaly, renal hypoplasia, and spastic paraplegia. By multipoint linkage analysis with markers spanning the entire X-chromosome we mapped the disease locus to a 28-Mb interval between Xp11.4 and Xq12, including the BCOR gene. A missense mutation in BCOR was described in a family with …
Two patients with EP300 mutations and facial dysmorphism different from the classic Rubinstein-Taybi syndrome
2009
Rubinstein-Taybi syndrome (RTS) is characterized by mental retardation, broad thumbs and great toes and a recognizable craniofacial phenotype. Causative mutations have been described in the CREBBP and EP300 genes. Here we present a 19-year-old woman and an unrelated 3-year-old boy, both with broad thumbs and halluces, but with facial aspects distinct from those of typical RTS. The woman had a marked learning disability, but no mental retardation. We identified a de novo c.7100delC mutation in EP300 (which predicts p.P2366RfsX35) in the woman and an apparently de novo c.638delG mutation in the boy, which predicts p.G213EfsX6. Mutations in EP300 are a known but rare cause of RTS. Only five ot…