Search results for "MUTATION"
showing 10 items of 2830 documents
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…
The link between mitochondrial DNA hypervariable segment I heteroplasmy and ageing among genetically unrelated Latvians
2011
International audience; Various studies have demonstrated that mitochondrial DNA (mtDNA) heteroplasmy tends to increase with age and that the observed frequency of heteroplasmy among populations mostly depends on the way it is measured. Therefore, we investigated age-related association on the presence of mtDNA heteroplasmy within the hypervariable segment 1 (HVS-I) in a selected study group. The study group consisted of 300 maternally unrelated Latvians ranging in age from 18 to over 90years. To determine the optimal method for mtDNA heteroplasmy detection, three approaches were used: (i) SURVEYORTM Mutation Detection Kit, (ii) sequencing and (iii) denaturing gradient-gel electrophoresis (…
NDST1 missense mutations in autosomal recessive intellectual disability.
2014
NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families. It encodes a bifunctional GlcNAc N-deacetylase/N-sulfotransferase with important functions in heparan sulfate biosynthesis. In mice, Ndst1 is crucial for embryonic development and homozygous null mutations are perinatally lethal. We now report on two additional unrelated families with homozygous missense NDST1 mutations. All mutations described to date predict the substitution of conserved amino acids in the sulfotransferase domain, and mutation modeling predicts drastic alterations in the local protein conformation. Comparing the four families, we noticed significant overlap in …
A series of West European patients with severe cardiac and skeletal myopathy associated with a de novo R406W mutation in desmin.
2003
Desminopathy is a familial or sporadic cardiac and skeletal muscular dystrophy associated with mutations in desmin. We have previously characterized a de novo desmin R406W mutation in a patient of European origin with early onset muscle weakness in the lower extremities and atrioventricular conduction block requiring a permanent pacemaker. The disease relentlessly progressed resulting in severe incapacity within 5 years after onset. We have now identified three other patients with early onset rapidly progressive cardiac and skeletal myopathy caused by this same desmin R406W mutation. The mutation was present in each studied patient, but not in their parents or other unaffected family member…
Efficacy and complications associated with a modified inferior alveolar nerve block technique. A randomized, triple-blind clinical trial
2014
Objectives: To compare the efficacy and complication rates of two different techniques for inferior alveolar nerve blocks (IANB). Study Design: A randomized, triple-blind clinical trial comprising 109 patients who required lower third molar removal was performed. In the control group, all patients received an IANB using the conventional Halsted technique, whereas in the experimental group, a modified technique using a more inferior injection point was performed. Results: A total of 100 patients were randomized. The modified technique group showed a significantly higher onset time in the lower lip and chin area, and was frequently associated to a lingual electric discharge sensation. Three f…
Intrathecal somatic hypermutation of IgM in multiple sclerosis and neuroinflammation
2014
Intrathecal oligoclonal bands of the cerebrospinal fluid are considered the most important immunological biomarkers of multiple sclerosis. They typically consist of clonally expanded IgG antibodies that underwent affinity maturation during sustained stimulation by largely unknown antigens. In addition, ∼40% of patients with multiple sclerosis have oligoclonal bands that consist of expanded IgM antibodies. We investigated the molecular composition of IgM- and IgG-chains from cerebrospinal fluid of 12 patients with multiple sclerosis, seven patients with other neurological diseases, and eight healthy control subjects by high-throughput deep-sequencing and single-cell PCR. Further, we studied …
REEP1 mutation spectrum and genotype/phenotype correlation in hereditary spastic paraplegia type 31.
2008
Contains fulltext : 71291.pdf (Publisher’s version ) (Closed access) Mutations in the receptor expression enhancing protein 1 (REEP1) have recently been reported to cause autosomal dominant hereditary spastic paraplegia (HSP) type SPG31. In a large collaborative effort, we screened a sample of 535 unrelated HSP patients for REEP1 mutations and copy number variations. We identified 13 novel and 2 known REEP1 mutations in 16 familial and sporadic patients by direct sequencing analysis. Twelve out of 16 mutations were small insertions, deletions or splice site mutations. These changes would result in shifts of the open-reading-frame followed by premature termination of translation and haploins…
Extremely High Mutation Rate of HIV-1 In Vivo.
2015
Rates of spontaneous mutation critically determine the genetic diversity and evolution of RNA viruses. Although these rates have been characterized in vitro and in cell culture models, they have seldom been determined in vivo for human viruses. Here, we use the intrapatient frequency of premature stop codons to quantify the HIV-1 genome-wide rate of spontaneous mutation in DNA sequences from peripheral blood mononuclear cells. This reveals an extremely high mutation rate of (4.1 ± 1.7) × 10−3 per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes …
Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia
2006
Skeletal dysplasias are difficult to diagnose for the nonexpert. In a previous study of patients with multiple epiphyseal dysplasia (MED), we identified cartilage oligomeric matrix protein (COMP) mutations in only 36% of cases and suspected that the low-mutation detection rate was partially due to misdiagnosis. We therefore instituted a clinical–radiographic review system, whereby all cases were evaluated by a panel of skeletal dysplasia experts (European Skeletal Dysplasia Network). Only those patients in whom the diagnosis of MED was confirmed by the panel were screened for mutations. Under this regimen the mutation detection rate increased to 81%. When clinical–radiological diagnostic cr…