Search results for "MUTATION"
showing 10 items of 2830 documents
PORCNmutations in focal dermal hypoplasia: coping with lethality
2009
The X-linked dominant trait focal dermal hypoplasia (FDH, Goltz syndrome) is a developmental defect with focal distribution of affected tissues due to a block of Wnt signal transmission from cells carrying a detrimental PORCN mutation on an active X-chromosome. Molecular characterization of 24 unrelated patients from different ethnic backgrounds revealed 23 different mutations of the PORCN gene in Xp11.23. Three were microdeletions eliminating PORCN and encompassing neighboring genes such as EBP, the gene associated with Conradi-Hunermann-Happle syndrome (CDPX2). 12/24 patients carried nonsense mutations resulting in loss of function. In one case a canonical splice acceptor site was mutated…
Wolcott-Rallison Syndrome
2004
Wolcott-Rallison syndrome (WRS) is a rare autosomal-recessive disorder characterized by the association of permanent neonatal or early-infancy insulin-dependent diabetes, multiple epiphyseal dysplasia and growth retardation, and other variable multisystemic clinical manifestations. Based on genetic studies of two inbred families, we previously identified the gene responsible for this disorder as EIF2AK3, the pancreatic eukaryotic initiation factor 2α (eIF2α) kinase. Here, we have studied 12 families with WRS, totalling 18 cases. With the exception of one case, all patients carried EIF2AK3 mutations resulting in truncated or missense versions of the protein. Exclusion of EIF2AK3 mutations in…
Epistasis between new mutations and genetic background and a test of genetic canalization.
2001
The importance for fitness of epistatic interactions among mutations is poorly known, yet epistasis can exert important effects on the dynamics of evolving populations. We showed previously that epistatic interactions are common between pairs of random insertion mutations in the bacterium Escherichia coli. In this paper, we examine interactions between these mutations and other mutations by transducing each of twelve insertion mutations into two genetic backgrounds, one ancestral and the other having evolved in, and adapted to, a defined laboratory environment for 10,000 generations. To assess the effect of the mutation on fitness, we allowed each mutant to compete against its unmutated cou…
Mutation screening of USH3 gene (clarin-1) in Spanish patients with Usher syndrome: low prevalence and phenotypic variability
2004
Usher syndrome type III is an autosomal recessive disorder clinically characterized by the association of retinitis pigmentosa (RP), variable presence of vestibular dysfunction and progressive hearing loss, being the progression of the hearing impairment the critical parameter classically used to distinguish this form from Usher syndrome type I and Usher syndrome type II. Usher syndrome type III clinical subtype is the rarest form of Usher syndrome in Spain, accounting only for 6% of all Usher syndrome Spanish cases. The gene responsible for Usher syndrome type III is named clarin-1 and it is thought to be involved in hair cell and photoreceptor cell synapses. Here, we report a screening fo…
Mutations in Myosin VIIA (MYO7A) and Usherin (USH2A) in Spanish patients with usher syndrome types I and II, respectively
2002
Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment and retinitis pigmentosa. Three clinical types are known (USH1, USH2 and USH3), and there is an extensive genetic heterogeneity, with at least ten genes implicated. The most frequently mutated genes are MYO7A, which causes USH1B, and usherin, which causes USH2A. We carried out a mutation analysis of these two genes in the Spanish population. Analysis of the MYO7A gene in patients from 30 USH1 families and sporadic cases identified 32% of disease alleles, with mutation Q821X being the most frequent. Most of the remaining variants are private mutations. With regard to USH2, mutation 2299delG was d…
Novel mutations including deletions of the entire OFD1 gene in 30 families with type 1 orofaciodigital syndrome : a study of the extensive clinical v…
2012
OFD1, now recognized as a ciliopathy, is characterized by malformations of the face, oral cavity and digits, and is transmitted as an X-linked condition with lethality in males. Mutations in OFD1 also cause X-linked Joubert syndrome (JBTS10) and Simpson-Golabi-Behmel syndrome type 2 (SGBS2). We have studied 55 sporadic and six familial cases of suspected OFD1. Comprehensive mutation analysis in OFD1 revealed mutations in 37 female patients from 30 families; 22 mutations have not been previously described including two heterozygous deletions spanning OFD1 and neighbouring genes. Analysis of clinical findings in patients with mutations revealed that oral features are the most reliable diagnos…
Chronic progressive external ophthalmoplegia with a novel mitochondrial DNA deletion and a mutation in the tRNALEU(UUR) gene
1999
Large-scale deletions and point mutations of the mitochondrial DNA are generally accepted as being involved in the pathogenesis of diseases associated with mitochondrial encephalomyopathies such as Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia (CPEO). We screened suspected patients using polymerase chain reaction techniques, Southern blot analyses, and muscle biopsy specimens. We report on a novel 4,953-base pair deletion associated with a familial occurrence of a tRNA Leu(UUR) T3250C point mutation in a young female patient clinically diagnosed with CPEO. This deletion is not flanked by direct repeats, so slip replication and homologous recombination do not seem li…
Mitochondrial DNA mutations in cancer--from bench to bedside.
2009
Mitochondria are cell organelles mostly known for their production of ATP through oxidative phosphorylation. As suggested over 70 years ago by O. Warburg and recently confirmed with molecular techniques, alterations in respiratory activity and mitochondrial DNA appear to be a common feature of malignant cells. Somatic mtDNA mutations have been reported in many types of cancer cells. MtDNA mutation pattern may enhance the specificity of cancer diagnostics, detection and prediction of tumor growth rate and patients' outcome. Therefore it may be used as a molecular cancer bio-marker. Nevertheless recently published papers list a large number of mitochondrial DNA mutations in many different can…
GroEL buffers against deleterious mutations
2002
GroEL, a heat-shock protein that acts as a molecular chaperone1, is overproduced in endosymbiotic but not in free-living bacteria2,3,4, presumably to assist in the folding of conformationally damaged proteins. Here we show that the overproduction of GroEL in Escherichia coli masks the effects of harmful mutations that have accumulated during a simulated process of vertical transmission. This molecular mechanism, which may be an adaptation to the bacterium's intracellular lifestyle, is able to rescue lineages from a progressive fitness decline resulting from the fixation of deleterious mutations under strong genetic drift5,6.
Sexual selection for genetic quality: disentangling the roles of male and female behaviour
2009
According to the good genes model of sexual selection, females choose males of good heritable genetic quality to obtain offspring with high fitness. However, better mating success of high-quality males can also be brought about by direct interference competition between males, or simply through elevated activity of high-quality males. We examined the roles of different processes leading to sexual selection for genetic quality in Drosophila montana. We manipulated genetic quality of male flies by inducing mutations with ionizing radiation. We then recorded the effects of inherited heterozygous mutations on several aspects of mating behaviour of males and females in two experiments. We found …