Search results for "deletion"
showing 10 items of 383 documents
Clinical manifestations and management of four children with Pearson syndrome.
2011
Pearson marrow-pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non-hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease.
Sequence variation in couch potato and its effects on life-history traits in a northern malt fly, Drosophila montana
2011
Abstract Couch potato ( cpo ) has previously been connected to reproductive diapause in several insect species including Drosophila melanogaster , where it has been suggested to provide a link between the insulin signalling pathway and the hormonal control of diapause. In the first part of the study we sequenced nearly 3.6 kb of this gene in a northern Drosophila species ( Drosophila montana ) with a robust photoperiodically determined diapause and found several types of polymorphisms along the sequenced area. We also found variation among five Drosophila virilis group species in the length of the 5th exon of cpo and in the site of the stop codon at the end of this exon. The second part of …
A novel two base pair deletion in the factor V gene associated with severe factor V deficiency
2001
We studied a family in which the proband, a 13-year-old boy, had unmeasurable plasma levels of coagulation factor V antigen and activity. Clinical symptoms were severe, with several episodes of haemorrhages in the mucosal tracts (gastrointestinal, nose and urinary) and recurrent haemarthroses that caused permanent arthropathy. Sequence analysis of the factor V gene demonstrated the presence of a novel 2 base pair (bp) homozygous deletion in exon 13 at positions 2833-2834. This mutation, present in the heterozygous state in the asymptomatic mother and absent in the healthy brother, introduced a frameshift and a premature stop at codon 900. This would predict the synthesis of a truncated fact…
Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations
2014
Purpose: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. Methods: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. Results: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic h…
RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis.
2012
The function of cytosine-C5 methylation, a widespread modification of tRNAs, has remained obscure, particularly in mammals. We have now developed a mouse strain defective in cytosine-C5 tRNA methylation, by disrupting both the Dnmt2 and the NSun2 tRNA methyltransferases. Although the lack of either enzyme alone has no detectable effects on mouse viability, double mutants showed a synthetic lethal interaction, with an underdeveloped phenotype and impaired cellular differentiation. tRNA methylation analysis of the double-knockout mice demonstrated complementary target-site specificities for Dnmt2 and NSun2 and a complete loss of cytosine-C5 tRNA methylation. Steady-state levels of unmethylate…
RNA methylation by Dnmt2 protects transfer RNAs against stress-induced cleavage
2010
The covalent modification of nucleic acids plays an important role in regulating the functions of DNA and RNA. DNA modifications have been analyzed in considerable detail, and the characterization of (cytosine-5) DNA methylation has been crucial for understanding the molecular basis of epigenetic gene regulation (Klose and Bird 2006). (Cytosine-5) methylation has also been documented in various RNA species, including tRNA, but the function of RNA methylation has not been firmly established yet (Motorin et al. 2010). Dnmt2 proteins were originally assigned to the DNA methyltransferase family, because of their strong sequence conservation of catalytic DNA methyltransferase motifs (Okano et al…
Association between the polymorphism of CCR5 and Alzheimer's disease: results of a study performed on male and female patients from Northern Italy.
2007
Alzheimer's disease (AD) is the most common cause of dementia in Western society. The prevalence of AD is greater in women than in men, largely due to longevity and survival differences favoring women. However, some studies suggest that incidence rates may really be increased in women. One possible factor influencing AD incidence in women is the loss of ovarian estrogens production after menopause, which might be involved in AD pathogenesis. Estrogens seem to influence some neuronal functions. Many of these actions appear beneficial (i.e., neuroprotective action against a variety of insults, as oxidative stress, and reduction of beta-amyloid plaques formation). Furthermore, several studies …
Disruption of the ASTN2 / TRIM32 locus at 9q33.1 is a risk factor in males for Autism Spectrum Disorders, ADHD and other neurodevelopmental phenotypes
2014
Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions o…
The Drosophila ACP65A cuticle gene: deletion scanning analysis of cis-regulatory sequences and regulation by DHR38.
2005
The regulatory sequences of the Drosophila ACP65A cuticle gene were analyzed in vivo in transgenic flies, using both fusion genes constructs and transposase-mediated deletions within a P element containing ACP65A regulatory sequences fused to the lacZ gene (deletion scanning). The sequences located between −594 and +161 are sufficient to confer both temporal and spatial expression specificities, indicating the presence of tissue-specific enhancers and response elements to hormone-induced factors. In addition, timing of expression and tissue-specificity appear to be controlled by distinct cis-regulatory elements, which suggests the existence of independent hormonal and tissue-specific signal…
Molecular Basis of Hereditary C1q Deficiency
1998
Abstract Complete selective deficiencies of the complement component C1q are rare genetic disorders which are associated with recurrent infections and a high prevalence of lupus erythematosus-like symptoms. The improvements in molecular biology techniques have facilitated the analysis of such genetic defects to a great extend. To date the basis of C1q deficiencies from 13 families have been studied at the genetic level. In each case single base mutations leading to either termination codons, frame shift or amino acid exchanges were thought to be responsible for these defects as no other aberrations were found. In addition to DNA analysis, conventional immunochemical and biochemical methods …