Search results for "Exon"
showing 10 items of 437 documents
Identification of a novel mutation in the alpha-galactosidase A gene in patients with Fabry disease.
2012
Abstract Objectives Mutation analysis of the alpha-galactosidase A (GLA) gene is a valuable tool for the diagnosis of affected families. In our work, we analyze about one thousand samples per year from patients suspected of having Fabry disease (FD). Design and methods We carried out high resolution melting analysis (HRM) and DNA sequencing of all the exons of the GLA gene. We also assayed the alpha-galactosidase A activity in patients' blood. Results In some members of one family, we identified a new mutation in the GLA gene, c.614delC. This is a deletion of a single nucleotide, a cytosine, in exon 4 of the gene which causes a frameshift mutation. Conclusions Patients with the c.614delC mu…
Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia
2010
Mutations in the SPG4 gene are the most common causes of hereditary spastic paraplegia (HSP) accounting for up to 40% of autosomal dominant (AD) forms and 12-18% of sporadic cases. The phenotype associated with HSP due to mutations in the SPG4 gene tends to be pure. There is increasing evidence, however, of patients with complicated forms of spastic paraplegia in which SPG4 mutations were identified. A cohort of 38 unrelated Italian patients with spastic paraplegia, of which 24 had a clear dominant inheritance and 14 were apparently sporadic, were screened for mutations in the SPG4 gene.We identified 11 different mutations, six of which were novel (p.Glu143GlyfsX8, p.Tyr415X, p.Asp548Asn, c…
Intragenic deletions of IL1RAPL1: Report of two cases and review of the literature
2010
IL1RAPL1 (interleukin-1 receptor accessory protein-like 1) located at Xp21.3-22.1 has repeatedly been shown to be deleted in patients with a contiguous gene syndrome also affecting neighboring genes, in particular DMD (dystrophin), DAX-1 (NR0B1, nuclear receptor subfamily 0, group B, member 1), and GK (glycerol kinase). In contrast, intragenic deletions of IL1RAPL1 or other mutations or cytogenetic aberrations affecting IL1RAPL1 have only rarely been identified. Up to date, they have mostly been associated with nonspecific mental retardation (MRX). We report on two nonrelated patients with MR and additional dysmorphic features who both show intragenic deletions of IL1RAPL1, one of them bein…
Molecular, genetic, and functional analysis of homozygous C8 beta-chain deficiency in two siblings.
1998
Abstract C8 deficiency is associated with an increased susceptibility to neisserial infections. We present a case of an 11 year old boy who suffered from infection with Neisseria meningitidis . Medical history of the patient and his family ( n = 5) did not indicate any previous immunodeficiency symptoms. Results from the analysis of phagocyte and lymphocyte functions were within the normal range. No hemolytic activities of the classical (CH50) and the alternative (APH50) pathways of complement were measurable, and SC5b-9 protein complexes could not be detected in the patient's plasma. Further analysis by highly sensitive ELISA and functional assays revealed a complete deficiency of C8. Upon…
Resistance to thyroid hormone in a family caused by a new point mutation L330S in the thyroid receptor (TR) beta gene.
1997
Resistance to thyroid hormone (RTH) is an inherited defect manifesting as variable tissue hyporesponsiveness to thyroid hormone, usually caused by mutations in the thyroid hormone receptor beta (TR beta) gene. Up to now 78 mutations in this gene have been identified, mostly clustered in two regions located in exon 9 and 10. We describe a new point mutation replacing the normal thymidine-1274 with a cytosine that results in the substitution of the normal leucine-330 with a serine (L330S) in the receptor protein. This mutation was identified in an 11-year-old boy who presented with symptoms and signs suggestive of both hyperthyroidism and hypothyroidism. Interestingly a mutation in the same c…
A Novel Deletion in the Thyrotropin Beta-Subunit Gene Identified by Array Comparative Genomic Hybridization Analysis Causes Central Congenital Hypoth…
2014
<b><i>Background:</i></b> Isolated central congenital hypothyroidism (ICCH) is rare but important. Most ICCH patients are diagnosed later, which results in severe growth failure and intellectual disability. <b><i>Objective:</i></b> We describe a boy with ICCH due to a large homozygous <i>TSHβ </i>gene deletion. <b><i>Results:</i></b> A 51-day-old male Turkish infant, whose parents were first cousins, was admitted for evaluation of prolonged jaundice. His clinical appearance was compatible with hypothyroidism. Venous thyrotropin (TSH) was undetectably low, with a subsequent low free T4 and a low free T3, sugg…
Gain of MYCN region in a Wilms tumor-derived xenotransplanted cell line.
2010
Wilms tumor is one of the most common pediatric malignant tumors of the kidney. Although the WT1 gene, located at 11p13, has been proven to be implicated in the development of Wilms tumor, other genes such as MYCN are also involved. The purpose of this study is to genetically characterize a Wilms tumor metastasis xenotransplanted in nude mice. Immunogenotype evolution of the xenografts material was monitored for 29 months using molecular techniques, fluorescent in situ hybridization and multiplex ligation-dependent probe amplification, in addition to immunohistochemistry in tissue microarrays. Genetic alterations present in the original tumor and retained in the xenotransplanted tumor were …
2-Methoxyestradiol confers neuroprotection and inhibits a maladaptive HIF-1α response after traumatic brain injury in mice
2014
HIF-1α is pivotal for cellular homeostasis in response to cerebral ischemia. Pharmacological inhibition of HIF-1α may reduce secondary brain damage by targeting post-translational mechanisms associated with its proteasomal degradation and nuclear translocation. This study examined the neuroprotective effects of 2-methoxyestradiol (2ME2), the involved HIF-1α-dependent response, and alternative splicing in exon 14 of HIF-1α (HIF-1α∆Ex14) after traumatic brain injury (TBI) in mice. Intraperitoneal 2ME2 administration 30 min after TBI caused a dose-dependent reduction in secondary brain damage after 24 h. 2ME2 was physiologically tolerated, showed no effects on immune cell brain migration, and …
Molecular, Genetic and Epidemiologic Studies on Selective Complete C1q Deficiency in Turkey
2000
Selective complete C1q deficiencies (SCDC1q) of the complement component C1q are rare genetic disorders with high prevalence of lupus-erythematosus-like symptoms and recurrent infections. Among the 41 published cases from 23 families, 10 derive from 6 Turkish families. One particular mutation leading to a stop codon in the C1q A gene was first identified in members of a Gypsy family from the Slovac Republic. Later the same mutation has been found in all cases in four SCDC1q families from Turkey suggesting that one particular defective allele may be present in the populations of Southeastern Europe and Turkey. This study was undertaken to investigate the frequency of C-->T mutation in exon I…
USH3A transcripts encode clarin-1, a four-transmembrane-domain protein with a possible role in sensory synapses.
2002
Usher syndrome type 3 (USH3) is an autosomal recessive disorder characterised by the association of post-lingual progressive hearing loss, progressive visual loss due to retinitis pigmentosa and variable presence of vestibular dysfunction. Because the previously defined transcripts do not account for all USH3 cases, we performed further analysis and revealed the presence of additional exons embedded in longer human and mouse USH3A transcripts and three novel USH3A mutations. Expression of Ush3a transcripts was localised by whole mount in situ hybridisation to cochlear hair cells and spiral ganglion cells. The full length USH3A transcript encodes clarin-1, a four-transmembrane-domain protein…