当前位置： SCI文献检索 > HUMAN GENETICS期刊下所有文献 > Altered mitochondrial function in cells carrying a premutation or unmethylated full mutation of the FMR1 gene.

Altered mitochondrial function in cells carrying a premutation or unmethylated full mutation of the FMR1 gene.

Abstract：

:Fragile X-related disorders are due to a dynamic mutation of the CGG repeat at the 5' UTR of the FMR1 gene, coding for the RNA-binding protein FMRP. As the CGG sequence expands from premutation (PM, 56-200 CGGs) to full mutation (> 200 CGGs), FMRP synthesis decreases until it is practically abolished in fragile X syndrome (FXS) patients, mainly due to FMR1 methylation. Cells from rare individuals with no intellectual disability and carriers of an unmethylated full mutation (UFM) produce slightly elevated levels of FMR1-mRNA and relatively low levels of FMRP, like in PM carriers. With the aim of clarifying how UFM cells differ from CTRL and FXS cells, a comparative proteomic approach was undertaken, from which emerged an overexpression of SOD2 in UFM cells, also confirmed in PM but not in FXS. The SOD2-mRNA bound to FMRP in UFM more than in the other cell types. The high SOD2 levels in UFM and PM cells correlated with lower levels of superoxide and reactive oxygen species (ROS), and with morphological anomalies and depolarization of the mitochondrial membrane detected through confocal microscopy. The same effect was observed in CTRL and FXS after treatment with MC2791, causing SOD2 overexpression. These mitochondrial phenotypes reverted after knock-down with siRNA against SOD2-mRNA and FMR1-mRNA in UFM and PM. Overall, these data suggest that in PM and UFM carriers, which have high levels of FMR1 transcription and may develop FXTAS, SOD2 overexpression helps to maintain low levels of both superoxide and ROS with signs of mitochondrial degradation.

journal_name

Hum Genet

journal_title

Human genetics

authors

Nobile V,Palumbo F,Lanni S,Ghisio V,Vitali A,Castagnola M,Marzano V,Maulucci G,De Angelis C,De Spirito M,Pacini L,D'Andrea L,Ragno R,Stazi G,Valente S,Mai A,Chiurazzi P,Genuardi M,Neri G,Tabolacci E

doi

10.1007/s00439-019-02104-7

subject

Has Abstract

pub_date

2020-02-01 00:00:00

pages

227-245

issue

2

eissn

0340-6717

issn

1432-1203

pii

10.1007/s00439-019-02104-7

journal_volume

139

pub_type

杂志文章

相关文献

HUMAN GENETICS文献大全
  • A case of Shwachman syndrome with increased spontaneous chromosome breakage.

    abstract：:In a patient with Shwachman syndrome, a high incidence of chromosome breakage was found. Chromosome studies done on three occasions on the patient's PHA-stimulated peripheral blood lymphocytes showed elevated frequencies of spontaneous chromosome aberrations compared with those in normal individuals. The patient's lym...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00284489

    authors： Tada H,Ri T,Yoshida H,Ishimoto K,Kaneko M,Yamashiro Y,Shinohara T

    更新日期：1987-11-01 00:00:00

  • Meiotic segregation analysis of a 14;21 Robertsonian translocation carrier by fluorescence in situ hybridization.

    abstract：:Meiotic segregation of chromosomes 14 and 21 in sperm from a 14;21 Robertsonian translocation carrier was analyzed with dual-color FISH using two locus-specific DNA probes (Tel 14q and LSI 21). The frequency of normal or chromosomally balanced sperm, resulting from alternate segregation, was 88.42%. The frequency of u...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s004390051027

    authors： Honda H,Miharu N,Samura O,He H,Ohama K

    更新日期：2000-02-01 00:00:00

  • Sperm rates of 7q11.23, 15q11q13 and 22q11.2 deletions and duplications: a FISH approach.

    abstract：:Genomic disorders are human diseases caused by meiotic chromosomal rearrangements of unstable regions flanked by Low Copy Repeats (LCRs). LCRs act as substrates for Non-Allelic Homologous Recombination (NAHR) leading to deletions and duplications. The aim of this study was to assess the basal frequency of deletions an...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-010-0894-4

    authors： Molina O,Anton E,Vidal F,Blanco J

    更新日期：2011-01-01 00:00:00

  • Sensitivity of Bloom's syndrome lymphocytes to ethyl methanesulfonate.

    abstract：:Ethyl methanesulfonate induced several times as many sister chromatid exchanges (SCE's) in lymphocytes from individuals affected with Bloom's syndrome as in lymphocytes from controls or heterozygotes. In cultures of cells from an individual with Bloom's syndrome who had two populations of lymphocytes circulating in hi...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00390236

    authors： Krepinsky AB,Heddle JA,German J

    更新日期：1979-01-01 00:00:00

  • The CLCA gene locus as a modulator of the gastrointestinal basic defect in cystic fibrosis.

    abstract：:To determine whether the CLCA gene family of calcium-activated chloride channels is a modulator of the basic defect of cystic fibrosis (CF), an association study was performed with polymorphic microsatellite markers covering a 40-Mbp region spanning the CLCA gene locus on human chromosome 1p in CF patients displaying ...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-004-1190-y

    authors： Ritzka M,Stanke F,Jansen S,Gruber AD,Pusch L,Woelfl S,Veeze HJ,Halley DJ,Tümmler B

    更新日期：2004-11-01 00:00:00

  • Deletion mapping of 39 random isolated Y-chromosome DNA fragments.

    abstract：:Thirty-nine recombinants isolated from a Y chromosome-specific library were deletion mapped. Seven deletion intervals were defined by hybridization of probes to DNA of eight individuals with aberrant Y chromosomes. Extreme cytogenetic limits of the deletion intervals were determined by in situ hybridization of one pro...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00193197

    authors： Oosthuizen CJ,Herbert JS,Vermaak LK,Brusnicky J,Fricke J,du Plessis L,Retief AE

    更新日期：1990-07-01 00:00:00

  • Spectrum of large copy number variations in 26 diverse Indian populations: potential involvement in phenotypic diversity.

    abstract：:Copy number variations (CNVs) have provided a dynamic aspect to the apparently static human genome. We have analyzed CNVs larger than 100 kb in 477 healthy individuals from 26 diverse Indian populations of different linguistic, ethnic and geographic backgrounds. These CNVRs were identified using the Affymetrix 50K Xba...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-011-1050-5

    authors： Gautam P,Jha P,Kumar D,Tyagi S,Varma B,Dash D,Mukhopadhyay A,Indian Genome Variation Consortium.,Mukerji M

    更新日期：2012-01-01 00:00:00

  • Intracellular phenylalanine and tyrosine concentrations in 19 heterozygotes for phenylketonuria (PKU) and 26 normals. Do the higher values in heterozygotes explain their lowered intellectual level?

    abstract：:Intracellular phenylalanine and tyrosine was determined in lymphocytes of 10 heterozygotes (parents) for PKU and in 26 randomly collected apparently normal persons. In cells from the heterozygotes the concentrations of both phenylalanine and tyrosine were higher than in those from the normals, the difference being sta...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00569353

    authors： Thalhammer O,Lubec G,Königshofer H

    更新日期：1979-07-18 00:00:00

  • Polymorphism of the pentanucleotide repeat d(AAAAT) within intron 1 of the human tumor suppressor gene p53 (17p13.1).

    abstract：:DyeDeoxy terminator cycle sequencing of allele-specific polymerase chain reaction products has shown that there is a highly polymorphic d(AAAAT) pentanucleotide repeat within the first intron of the human p53 gene. This provides a genetic marker for tumor suppressor p53 gene alterations. ...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00208983

    authors： Hahn M,Fislage R,Pingoud A

    更新日期：1995-04-01 00:00:00

  • Molecular defects in the alpha-N-acetylglucosaminidase gene in Italian Sanfilippo type B patients.

    abstract：:Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is a rare autosomal recessive disorder characterized by the inability to degrade heparan sulfate because of a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). We performed mutation screening in a group of 20 patients, identyifing 28 mutat...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s004390000429

    authors： Tessitore A,Villani GR,Di Domenico C,Filocamo M,Gatti R,Di Natale P

    更新日期：2000-12-01 00:00:00

  • Genomics of alternative splicing: evolution, development and pathophysiology.

    abstract：:Alternative splicing is a major cellular mechanism in metazoans for generating proteomic diversity. A large proportion of protein-coding genes in multicellular organisms undergo alternative splicing, and in humans, it has been estimated that nearly 90 % of protein-coding genes-much larger than expected-are subject to ...

    journal_title：Human genetics

    pub_type： 杂志文章,评审

    doi：10.1007/s00439-013-1411-3

    authors： Gamazon ER,Stranger BE

    更新日期：2014-06-01 00:00:00

  • APOH interacts with FTO to predispose to healthy thinness.

    abstract：:We identified eight candidate thinness predisposition variants from the Illumina HumanExome chip genotyped on members of pedigrees selected for either healthy thinness or severe obesity. For validation, we tested the candidates for association with healthy thinness in additional pedigree members while accounting for e...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-015-1629-3

    authors： Hasstedt SJ,Coon H,Xin Y,Adams TD,Hunt SC

    更新日期：2016-02-01 00:00:00

  • The T-->C mutation at position +96 of the untranslated region 3' to the terminating codon of the beta-globin gene is a rare polymorphism that does not cause a beta-thalassemia as previously ascribed.

    abstract：:We have observed a T-->C mutation at position +96 of the untranslated region 3' to the terminating codon of the beta-globin gene in members of two Czech families and one black family. Data from initial studies suggested that this change was the cause of a beta-thalassemia, but continued analyses have provided convinci...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00218918

    authors： Divoky V,Baysal E,Oner R,Cürük MA,Walker EL 3rd,Indrak K,Huisman TH

    更新日期：1994-01-01 00:00:00

  • Nucleoli of cultured human lymphocytes. II. Nuceolar fusion and its relation to acrocentric association.

    abstract：:Nucleolar fusion and nucleolus formation occurred simultaneously, immediately after mitosis, in cultured human lymphocytes. Evidence is presented that in late telophase and post-telophase, the individual nucleolar organising site includes two components, represented in post-telophase by the nucleolus and its attached ...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00291307

    authors： Gani R

    更新日期：1978-06-27 00:00:00

  • Complex translocation t(9;21)(9;22)(q12p13)(q12q11) in the family of a child with 9p trisomy syndrome.

    abstract：:A case of partial trisomy 9 is described in a mentally retarded and dysmorphic child, confirming that this chromosome unbalance results in a characteristic clinical entity. This trisomy arose through aberrant segregation of translocation chromosome during meiosis in the patient's mother, who is a balanced heterozygote...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00447289

    authors： Dallapiccola B,Bollea G,Mazzilli C,Gandini E

    更新日期：1976-07-07 00:00:00

  • Hereditary triosephosphate isomerase (TPI) deficiency: two severely affected brothers one with and one without neurological symptoms.

    abstract：:A 13-year-old Hungarian boy (B.J.Jr.) with congenital haemolytic anaemia (CHA) and hyperkinetic torsion dyskinesia was found to have severe triose-phosphate isomerase (TPI) deficiency. One of his two brothers (A.J.), a 23-year-old amateur wrestler, has CHA as well, but no neurological symptoms. Both have less than 10%...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00216456

    authors： Hollán S,Fujii H,Hirono A,Hirono K,Karro H,Miwa S,Harsányi V,Gyódi E,Inselt-Kovács M

    更新日期：1993-11-01 00:00:00

  • Phenotype-genotype correlations and emerging pathways in ocular anterior segment dysgenesis.

    abstract：:Disorders of the anterior segment of the eye encompass a variety of clinical presentations including aniridia, Axenfeld and Rieger anomalies, primary congenital glaucoma, Peters anomaly, as well as syndromal associations. These conditions have a significant impact on vision due to disruption of the visual axis, and al...

    journal_title：Human genetics

    pub_type： 杂志文章,评审

    doi：10.1007/s00439-018-1935-7

    authors： Ma AS,Grigg JR,Jamieson RV

    更新日期：2019-09-01 00:00:00

  • Characterization of a partial pseudogene homologous to the Hermansky-Pudlak syndrome gene HPS-1; relevance for mutation detection.

    abstract：:The HPS-1 gene is the first gene found to be responsible for the autosomal recessive disorder Hermansky-Pudlak syndrome (HPS). HPS is characterized by oculocutaneous albinism, a platelet storage pool deficiency, and ceroid lipofuscinosis. The HPS-1 gene has been mapped to chromosome 10q23.1-23.3 and encodes a 79-kDa p...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s004390051053

    authors： Huizing M,Anikster Y,Gahl WA

    更新日期：2000-03-01 00:00:00

  • Geroderma osteodysplastica. A report of two affected families.

    abstract：:This paper describes two families in which four boys and two girls were affected with geroderma osteodysplastica. The major features of this syndrome include a droopy, jowly, prematurely aged appearance that has been likened by previous authors to the dwarfs in Walt Disney's 'Snow White.' Also, their skin lacks normal...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00272192

    authors： Hunter AG,Martsolf JT,Baker CG,Reed MH

    更新日期：1978-02-16 00:00:00

  • A novel trinucleotide repeat expansion at chromosome 3q26.2 identified by a CAG/CTG repeat expansion detection array.

    abstract：:CAG/CTG repeat expansions cause at least 12 different neurological disorders, and additional disorders of this type probably exist. Using the repeat expansion detection (RED) assay, we identified an expanded CAG/CTG repeat in a 50-year-old woman with an autosomal dominant syndrome with prominent progressive sensory ne...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-006-0207-0

    authors： Holmes SE,Wentzell JS,Seixas AI,Callahan C,Silveira I,Ross CA,Margolis RL

    更新日期：2006-09-01 00:00:00

  • Gm allotypes and racial admixture in two Brazilian populations.

    abstract：:The Gm types of 515 inhabitants of Belém and 395 inhabitants of Porto Alegre, Brazil were studied in an attempt to quantitatively estimate ethnic parental contributions. The people from Belém can be characterized as 24% black, 22% Indian, and 54% Caucasian. The Porto Alegre blacks seem to have inherited as much as 53%...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/BF00289458

    authors： Schneider H,Salzano FM

    更新日期：1979-01-01 00:00:00

  • Two novel mutations in the aquaporin-2 and the vasopressin V2 receptor genes in patients with congenital nephrogenic diabetes insipidus.

    abstract：:The vasopressin V2 receptor (V2R) and the aquaporin-2 genes of two unrelated male patients with congenital nephrogenic diabetes insipidus were analyzed. The V2R gene of the patient of family 1 had the wild-type sequence. Consequently, the coding region of the aquaporin-2 gene including the exon-intron junctions was se...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s004390050264

    authors： Oksche A,Möller A,Dickson J,Rosendahl W,Rascher W,Bichet DG,Rosenthal W

    更新日期：1996-11-01 00:00:00

  • Analyses of genetic abnormalities in type I CD36 deficiency in Japan: identification and cell biological characterization of two novel mutations that cause CD36 deficiency in man.

    abstract：:To elucidate genetic abnormalities in type I CD36 deficiency, we analyzed 28 Japanese subjects whose platelets and monocytes/macrophages lacked CD36 on their surface. We identified two novel mutations in the CD36 gene. One was a complex deletion/insertion mutation, in which 3 bp, GAG, were deleted at nucleotide (nt) 8...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s004390100525

    authors： Kashiwagi H,Tomiyama Y,Nozaki S,Kiyoi T,Tadokoro S,Matsumoto K,Honda S,Kosugi S,Kurata Y,Matsuzawa Y

    更新日期：2001-06-01 00:00:00

  • Estimation of metabolic syndrome heritability in three large populations including full pedigree and genomic information.

    abstract：:Metabolic syndrome is a complex human disorder characterized by a cluster of conditions (increased blood pressure, hyperglycemia, excessive body fat around the waist, and abnormal cholesterol or triglyceride levels). Any of these conditions increases the risk of serious disorders such as diabetes or cardiovascular dis...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-019-02024-6

    authors： Graziano F,Biino G,Bonati MT,Neale BM,Do R,Concas MP,Vaccargiu S,Pirastu M,Terradura-Vagnarelli O,Cirillo M,Laurenzi M,Mancini M,Zanchetti A,Grassi M

    更新日期：2019-07-01 00:00:00

  • Refinement of the genetic cause of ATR-16.

    abstract：:Alpha thalassemia retardation associated with chromosome16 (ATR-16 syndrome) is defined as a contiguous gene syndrome resulting from haploinsufficiency of the alpha-globin gene cluster and genes involved in mental retardation (MR). To date, only few cases have been described which result from pure monosomy for a delet...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-007-0399-y

    authors： Harteveld CL,Kriek M,Bijlsma EK,Erjavec Z,Balak D,Phylipsen M,Voskamp A,di Capua E,White SJ,Giordano PC

    更新日期：2007-11-01 00:00:00

  • Genotype-phenotype correlations in families with deletions in the von Hippel-Lindau (VHL) gene.

    abstract：:Von Hippel-Lindau (VHL) disease is a hereditary tumor syndrome characterized by predisposition for bilateral and multi-centric hemangioblastoma in the retina and central nervous system, pheochromocytoma, renal cell carcinoma, and cysts in the kidney, pancreas, and epididymis. We describe five families for which direct...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s004390000265

    authors： Hes F,Zewald R,Peeters T,Sijmons R,Links T,Verheij J,Matthijs G,Leguis E,Mortier G,van der Torren K,Rosman M,Lips C,Pearson P,van der Luijt R

    更新日期：2000-04-01 00:00:00

  • Ectodermal dysplasia-cutaneous syndactyly syndrome maps to chromosome 7p21.1-p14.3.

    abstract：:Ectodermal dysplasia syndromes are genetically heterogeneous group of disorders involving one or more of the classical ectodermal appendages (hair, nail, teeth, sweat glands) in association with anomalies of other organs or systems. In the present study a novel form of ectodermal dysplasia syndrome, ectodermal dysplas...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-009-0640-y

    authors： Tariq M,Khan MN,Ahmad W

    更新日期：2009-05-01 00:00:00

  • Joint modeling of eQTLs and parent-of-origin effects using an orthogonal framework with RNA-seq data.

    abstract：:Extensive studies have been conducted on the analysis of genome function, especially on the expression quantitative trait loci (eQTL). These studies offered promising results for characterization of the functional sequencing variation and understanding of the basic processes of gene regulation. Parent of origin effect...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-020-02162-2

    authors： Deng S,Hardin J,Amos CI,Xiao F

    更新日期：2020-08-01 00:00:00

  • Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees.

    abstract：:To elucidate the mechanism of lipid metabolism in the genesis of essential hypertension (EH), we linked blood pressure (BP) phenotypes with the lipoprotein lipase (LPL) gene. Variance component and sib-pair linkage models were used to test the relationship of the polymorphisms in the LPL gene region and EH in 148 Chin...

    journal_title：Human genetics

    pub_type： 杂志文章

    doi：10.1007/s00439-004-1108-8

    authors： Yang W,Huang J,Ge D,Yao C,Duan X,Shen Y,Qiang B,Gu D

    更新日期：2004-06-01 00:00:00

  • Evidence for a modifying pathway in SMA discordant families: reduced SMN level decreases the amount of its interacting partners and Htra2-beta1.

    abstract：:Proximal spinal muscular atrophy (SMA) is a neuromuscular disorder caused by homozygous mutations of the SMN1 gene. SMN1 interacts with multiple proteins with functions in snRNP biogenesis, pre-mRNA splicing and presumably neural transport. SMN2, a nearly identical copy of SMN1, produces predominantly exon 7-skipped t...

    journal_title：Human genetics

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s00439-003-1025-2

    authors： Helmken C,Hofmann Y,Schoenen F,Oprea G,Raschke H,Rudnik-Schöneborn S,Zerres K,Wirth B

    更新日期：2003-12-01 00:00:00