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21.
Frameshift mutation in the survival motor neuron gene in a severe case of SMA type I 总被引:9,自引:9,他引:9
Brahe C; Clermont O; Zappata S; Tiziano F; Melki J; Neri G 《Human molecular genetics》1996,5(12):1971-1976
Recently, a spinal muscular atrophy (SMA) determining gene, termed survival
motor neuron (SMN) gene, has been isolated from the 5q13 region and found
deleted in most patients. A highly homologous copy of this gene has also
been isolated and located in a centromeric position. We have analyzed 158
patients (SMA types I-IV) and found deletions of SMN exon 7 in 96.8%.
Mutations other than gross deletions seem to be extremely rare. In one of
the undeleted SMA type I patients, a newborn who survived for only 42 days,
we detected a maternally inherited 5 bp microdeletion in exon 3, resulting
in a premature stop codon. By RT-PCR and long range PCR amplification we
were able to show that the deletion belongs to the SMN gene, rather than to
the centromeric copy, and that the proposita had no paternal SMN gene.
Analysis of the neuronal apoptosis inhibitor protein (NAIP) gene, which
maps close to SMN and has been proposed as a SMA modifying gene, suggests
the presence of at least one full-length copy. Haplotype analysis of
closely linked polymorphic markers suggests that the proposita also lacks
the maternally derived copy of the centromeric homologue of SMN supporting
the hypothesis that the severity of the phenotype might depend on the
reduced number of centromeric genes in addition to the frameshift mutation.
相似文献
22.
Libra M Capello D Gloghini A Laura P Berra E Cerri M Gasparotto D Franca S De Re V Gaidano G Carbone A 《The Journal of pathology》2005,206(1):87-91
Hepatitis C virus (HCV) and aberrant somatic hypermutation (SHM) have each been suggested to contribute to the development of B-cell non-Hodgkin's lymphoma (NHL). The incidence of PIM-1, PAX-5, RhoH/TTF, and c-MYC mutations in tumour biopsy specimens from 32 HCV-infected B-cell NHL patients was analysed to determine whether the extent of aberrant SHM among these patients differed from that previously reported for HCV-negative B-cell NHL patients. Mutation of PIM-1, PAX-5, RhoH/TTF, and c-MYC was detected in 4 (13%), 5 (16%), 4 (13%), and 4 (13%) of 32 samples, respectively. In HCV-positive B-cell NHL patients, the frequency of aberrant SHM was lower than that already found in HCV-negative B-cell NHL patients. This indicates that, unlike B-cell lymphomas from HCV-negative patients, aberrant SHM may not contribute significantly to malignant transformation in HCV-associated B-cell lymphomas. 相似文献
23.
Massa O Iafusco D D'Amato E Gloyn AL Hattersley AT Pasquino B Tonini G Dammacco F Zanette G Meschi F Porzio O Bottazzo G Crinó A Lorini R Cerutti F Vanelli M Barbetti F;Early Onset Diabetes Study Group of the Italian Society of Pediatric Endocrinology Diabetology 《Human mutation》2005,25(1):22-27
Permanent neonatal diabetes mellitus (PNDM) is a rare condition characterized by severe hyperglycemia constantly requiring insulin treatment from its onset. Complete deficiency of glucokinase (GCK) can cause PNDM; however, the genetic etiology is unknown in most PNDM patients. Recently, heterozygous activating mutations of KCNJ11, encoding Kir6.2, the pore forming subunit of the ATP-dependent potassium (K(ATP)) channel of the pancreatic beta-cell, were found in patients with PNDM. Closure of the K(ATP) channel exerts a pivotal role in insulin secretion by modifying the resting membrane potential that leads to insulin exocytosis. We screened the KCNJ11 gene in 12 Italian patients with PNDM (onset within 3 months from birth) and in six patients with non-autoimmune, insulin-requiring diabetes diagnosed during the first year of life. Five different heterozygous mutations were identified: c.149G>C (p.R50P), c.175G>A (p.V59M), c.509A>G (p.K170R), c.510G>C (p.K170N), and c.601C>T (p.R201C) in eight patients with diabetes diagnosed between day 3 and 182. Mutations at Arg50 and Lys170 residues are novel. Four patients also presented with motor and/or developmental delay as previously reported. We conclude that KCNJ11 mutations are a common cause of PNDM either in isolation or associated with developmental delay. Permanent diabetes of non autoimmune origin can present up to 6 months from birth in individuals with KCNJ11 and EIF2AK3 mutations. Therefore, we suggest that the acronym PNDM be replaced with the more comprehensive permanent diabetes mellitus of infancy (PDMI), linking it to the gene product (e.g., GCK-PDMI, KCNJ11-PDMI) to avoid confusion between patients with early-onset, autoimmune type 1 diabetes. 相似文献
24.
25.
Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity 总被引:2,自引:0,他引:2
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Hernández L Beà S Bellosillo B Pinyol M Falini B Carbone A Ott G Rosenwald A Fernández A Pulford K Mason D Morris SW Santos E Campo E 《The American journal of pathology》2002,160(4):1487-1494
Anaplastic large cell lymphomas are associated with chromosomal aberrations involving the anaplastic lymphoma kinase (ALK) gene at 2p23 that result in the expression of novel chimeric ALK proteins with transforming properties. In most of these tumors, the t(2;5)(p23;q35) generates the NPM-ALK fusion gene. However, several studies have now demonstrated that genes other than NPM may be fused to the ALK gene. We have recently described two different ALK rearrangements involving the TRK-fused gene (TFG) in which the same portion of ALK was fused to different length fragments of the 5' TFG region. These two rearrangements encoded chimeric proteins of 85 kd (TFG-ALK(S)) and 97 kd (TFG-ALK(L)), respectively. In this study, we have identified a new ALK rearrangement in which the catalytic domain of ALK was fused to a larger fragment of the TFG gene (TFG-ALK(XL)), encoding for a fusion protein of 113 kd. Genomic analysis of these three TFG-ALK rearrangements revealed that the TFG breakpoints occur at introns 3, 4, and 5, respectively, whereas the ALK breakpoints always occur in the same intron. No homologous regions or known recombination sequences were found in these regions. Transfection experiments using NIH-3T3 fibroblasts showed a similar transforming efficiency of TFG-ALK variants compared with NPM-ALK. In addition, in common with NPM-ALK, the TFG-ALK proteins formed stable complexes with the signaling proteins Grb2, Shc, and PLC-gamma. In conclusion, these findings indicate that the TFG may use a variety of intronic breakpoints in ALK rearrangements generating fusion proteins of different molecular weights, but with similar transforming potential than NPM-ALK. 相似文献
26.
Genes and translocations involved in POF 总被引:14,自引:0,他引:14
27.
Antonino Carbone Annunziata Gloghini Ivana Zanette Barbara Canal Aurora Rizzo Rachele Volpe 《Virchows Archiv : an international journal of pathology》1993,422(1):39-45
Summary The presence of Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg (HRS) cells, as detected using in situ hybridization (ISH) with biotinylatedBamHI V probes, along with the expression of EBV-encoded latent membrane protein (LMP) and vimentin was examined in paraffin-embedded sections of 39 immunomorphologically characterized cases of Hodgkin's disease (HD). ISH demonstrated EBV in HRS cells in 15 of 39 cases, whereas LMP expression was detected in 11 of 39 cases, only in the presence of EBV genome detection. With the exception of 1 case, in which HRS cells expressed B-cell-associated antigens, the LMP-positive cases included specimens in which HRS cells were of non-B, non-T phenotype. LMP expression showed a stronger association with lymphocyte depletion (LD) (3/3) and mixed cellularity (MC) (6/11) than with lymphocyte predominance (0/5) or nodular sclerosis (2/20) subtypes. Vimentin expression on HRS cells was found in all the LMP-expressing cases and only in a fraction (13/28) of LMP-negative cases. This study supports the view that HD represents a heterogeneous group of diseases also in terms of EBV association, LMP expression being strongly related to the aggressive LD and MC histological subtypes. In light of the supposed interactions between vimentin and LMP, their coexpression on HRS cells, as detected in this study, provides further evidence for a significant role of EBV in the development of a proportion of HD cases. 相似文献
28.
Fadda G Muie A Rufini V Ardito G Revelli L Fiorino MC Capelli A 《Endocrine pathology》2000,11(4):373-377
Cystic lesions of the thyroid are common findings. Although many thyroid cysts are of benign, some cases of hemorrhagic degenerative
changes occur in neoplastic nodules, mostly follicular neoplasms and papillary carcinomas. The occurrence of hemorrhagic changes
in medullary carcinomas has never been documented with aspirative cytological and histological pictures to the best of our
knowledge. A case of medullary thyroid carcinoma with a large central hemorrhagic cyst is described, and the literature regarding
the pathogenesis of this regression and the occurrence of cystic neoplasms in the thyroid is reviewed. 相似文献
29.
Markowska A Neri G Hochol A Nowak M Nussdorfer GG Malendowicz LK 《International journal of molecular medicine》2004,13(1):139-141
Leptin, an adipose tissue-secreted hormone, acts via several isoforms of specific receptors (Ob-Rs), which may variously interact with the native leptin molecule and its fragments. Evidence has been provided that leptin affects rat adrenal functions, but the results were rather conflicting depending on the experimental condition examined (e.g. regenerating vs. mature or immature adrenal gland). Hence, we investigated the effects of three subcutaneous injections of murine leptin(1-147) and several leptin fragments (3 nmol/100 g body weight; 28, 16 and 4 h before the sacrifice) on the secretory activity and growth of regenerating rat adrenal cortex. The following leptin fragments were tested: murine leptin(116-130), and human leptin fragments 150-167, 138-167, 93-105, 22-56 and [Tyr]26-39. Leptin(1-147) enhanced plasma concentration of both aldosterone and corticosterone. The blood level of aldosterone was raised by leptin(116-130), leptin(138-167) and leptin(93-105), and that of corticosterone by leptin(93-105) and Tyr-leptin(26-39). Metaphase index (stachmokinetic method with vincristine) was unaffected by leptin(1-147), and lowered by leptin(116-130), leptin(150-167) and leptin(138-167). Collectively, our findings allow us to conclude that leptin and leptin fragments enhance the secretory activity and inhibit the growth of regenerating rat adrenal cortex, the biological activity of leptin being located in the C-terminal segment of its molecule. 相似文献
30.
First report of capsule replacement among electrophoretic type 37 Neisseria meningitidis strains in Italy
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Stefanelli P Fazio C Neri A Sofia T Mastrantonio P 《Journal of clinical microbiology》2003,41(12):5783-5786
This report describes the C-to-B capsular switching in four Neisseria meningitidis strains belonging to the electrophoretic type 37 (ET-37) complex. In particular, one strain belonged to the new sequence type 1860, which was first detected in the year 2000 in Italy and is now frequently isolated. The presence of switched serogroup B strains deserves special attention if they prove as able to spread as their serogroup C progenitors belonging to the hypervirulent ET-37 complex. 相似文献