当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Functional analysis of paired box missense mutations in the PAX6 gene.

Functional analysis of paired box missense mutations in the PAX6 gene.

Abstract：

:Mutations in the human PAX6 gene produce various phenotypes, including aniridia, Peters' anomaly, autosomal dominant keratitis and familial foveal dysplasia. The various phenotypes may arise from different mutations in the same gene. To test this theory, we performed a functional analysis of two missense mutations in the paired domain: the R26G mutation, previously reported in a case of Peters' anomaly, and an unreported I87R mutation, which we identified in a patient with aniridia. While both the R26 and the I87 positions are conserved in the paired boxes of all known PAX genes, X-ray crystallography has shown that only R26 makes contact with DNA. We showed that the R26G mutant failed to bind a subset of paired domain binding sites but, surprisingly, bound other sites and successfully transactivated promoters containing those sites. In contrast, the I87R mutant had lost the ability to bind DNA at all tested sites and failed to transactivate promoters. Our data support the haploid-insufficiency hypothesis of aniridia, and the hypothesis that R26G is a hypomorphic allele.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Tang HK,Chao LY,Saunders GF

doi

10.1093/hmg/6.3.381

subject

Has Abstract

pub_date

1997-03-01 00:00:00

pages

381-6

issue

3

eissn

0964-6906

issn

1460-2083

pii

dda054

journal_volume

6

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • IFT52 mutations destabilize anterograde complex assembly, disrupt ciliogenesis and result in short rib polydactyly syndrome.

    abstract：:The short-rib polydactyly syndromes (SRPS) encompass a radiographically and genetically heterogeneous group of skeletal ciliopathies that are characterized by a long narrow chest, short extremities, and variable occurrence of polydactyly. Radiographic abnormalities include undermineralization of the calvarium, shorten...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw241

    authors： Zhang W,Taylor SP,Nevarez L,Lachman RS,Nickerson DA,Bamshad M,University of Washington Center for Mendelian Genomics Consortium.,Krakow D,Cohn DH

    更新日期：2016-09-15 00:00:00

  • The Leri-Weill and Turner syndrome homeobox gene SHOX encodes a cell-type specific transcriptional activator.

    abstract：:Functional impairment of the human homeobox gene SHOX causes short stature and Madelung deformity in Leri-Weill syndrome (LWS) and has recently been implicated in additional skeletal malformations frequently observed in Turner syndrome. To enhance our understanding of the underlying mechanism of action, we have establ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.26.3083

    authors： Rao E,Blaschke RJ,Marchini A,Niesler B,Burnett M,Rappold GA

    更新日期：2001-12-15 00:00:00

  • Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis.

    abstract：:Lysosomal neuraminidase is the key enzyme for the intralysosomal catabolism of sialylated glycoconjugates and is deficient in two neurodegenerative lysosomal disorders, sialidosis and galactosialidosis. Here we report the identification of eight novel mutations in the neuraminidase gene of 11 sialidosis patients with ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.18.2715

    authors： Bonten EJ,Arts WF,Beck M,Covanis A,Donati MA,Parini R,Zammarchi E,d'Azzo A

    更新日期：2000-11-01 00:00:00

  • Loss of LDAH associated with prostate cancer and hearing loss.

    abstract：:Great strides in gene discovery have been made using a multitude of methods to associate phenotypes with genetic variants, but there still remains a substantial gap between observed symptoms and identified genetic defects. Herein, we use the convergence of various genetic and genomic techniques to investigate the unde...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy310

    authors： Currall BB,Chen M,Sallari RC,Cotter M,Wong KE,Robertson NG,Penney KL,Lunardi A,Reschke M,Hickox AE,Yin Y,Wong GT,Fung J,Brown KK,Williamson RE,Sinnott-Armstrong NA,Kammin T,Ivanov A,Zepeda-Mendoza CJ,Shen J,Quade

    更新日期：2018-12-15 00:00:00

  • Genome-wide linkage analysis and evidence of gene-by-gene interactions in a sample of 362 multiplex Parkinson disease families.

    abstract：:Parkinson disease (PD) is the second most common neurodegenerative disorder. We studied 754 affected individuals, comprising 425 sibling pairs, to identify PD susceptibility genes. Screening of the parkin gene was performed in a subset of the sample having earlier age of PD onset or a positive LOD score with a marker ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg270

    authors： Pankratz N,Nichols WC,Uniacke SK,Halter C,Murrell J,Rudolph A,Shults CW,Conneally PM,Foroud T,Parkinson Study Group.

    更新日期：2003-10-15 00:00:00

  • Cholesterol regulates ABCD2 expression: implications for the therapy of X-linked adrenoleukodystrophy.

    abstract：:X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder with impaired very long-chain fatty acid (VLCFA) metabolism. The disease-associated ABCD1 (ALD) gene encodes a peroxisomal membrane protein, which belongs to the superfamily of ATP-binding cassette transporters. Several treatment regimes have...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/11.22.2701

    authors： Weinhofer I,Forss-Petter S,Zigman M,Berger J

    更新日期：2002-10-15 00:00:00

  • 15q11-13 GABAA receptor genes are normally biallelically expressed in brain yet are subject to epigenetic dysregulation in autism-spectrum disorders.

    abstract：:Human chromosome 15q11-13 is a complex locus containing imprinted genes as well as a cluster of three GABA(A) receptor subunit (GABR) genes-GABRB3, GABRA5 and GABRG3. Deletion or duplication of 15q11-13 GABR genes occurs in multiple human neurodevelopmental disorders including Prader-Willi syndrome (PWS), Angelman syn...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm014

    authors： Hogart A,Nagarajan RP,Patzel KA,Yasui DH,Lasalle JM

    更新日期：2007-03-15 00:00:00

  • Proximal deletions of the long arm of the Y chromosome suggest a critical region associated with a specific subset of characteristic Turner stigmata.

    abstract：:Turner syndrome is a complex human disorder that generally associates a 45,X karyotype to a female phenotype presenting with gonadal dysgenesis, short stature and a number of characteristic somatic features. It has been hypothesized that this specific phenotype was the consequence of the haploinsufficiency of some X-l...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.9.1565

    authors： Barbaux S,Vilain E,Raoul O,Gilgenkrantz S,Jeandidier E,Chadenas D,Souleyreau N,Fellous M,McElreavey K

    更新日期：1995-09-01 00:00:00

  • De novo mutation in the COL4A5 gene converting glycine 325 to glutamic acid in Alport syndrome.

    abstract：:Southern blot analysis of the COL4A5 gene in a 6 year old Italian Alport patient (proband VIZ) showed the loss of an MspI site that was present in the mother and control DNAs. PCR amplification and DNA sequencing revealed a single G-->A nucleotide change. The mutation results in substitution of a glutamic acid for a g...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/1.2.127

    authors： Renieri A,Seri M,Myers JC,Pihlajaniemi T,Massella L,Rizzoni G,De Marchi M

    更新日期：1992-05-01 00:00:00

  • A transcription map of the region containing the Huntington disease gene.

    abstract：:A transcription map of the Huntington disease gene region was generated by a direct cDNA selection strategy using genomic DNA from the 4p16.3 region surrounding the D4S95 and D4S127 loci. A total of 58 cDNA fragments were obtained from cDNAs derived from fetal brain, frontal cortex, liver and bone marrow following hyb...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/2.7.901

    authors： Rommens JM,Lin B,Hutchinson GB,Andrew SE,Goldberg YP,Glaves ML,Graham R,Lai V,McArthur J,Nasir J

    更新日期：1993-07-01 00:00:00

  • The Old World monkey DAZ (Deleted in AZoospermia) gene yields insights into the evolution of the DAZ gene cluster on the human Y chromosome.

    abstract：:The DAZ gene cluster on the human Y chromosome is a candidate for the Azoospermia Factor (AZFc). According to the current evolutionary model, the DAZ cluster derived from the autosomal homolog DAZL1 through duplications and rearrangements and is confined to Old World monkeys, apes and humans. To study functional and e...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/8.11.2017

    authors： Gromoll J,Weinbauer GF,Skaletsky H,Schlatt S,Rocchietti-March M,Page DC,Nieschlag E

    更新日期：1999-10-01 00:00:00

  • Myotonia levior is a chloride channel disorder.

    abstract：:The group of dominant non-dystrophic myotonias, comprising disorders characterized by clinically similar forms of myogenic muscle stiffness, is genetically inhomogeneous. Dominant myotonia congenita (Thomsen's disease) is linked to CLCN1, the gene encoding the major muscle chloride channel, localized on chromosome 7q3...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.8.1397

    authors： Lehmann-Horn F,Mailänder V,Heine R,George AL

    更新日期：1995-08-01 00:00:00

  • AAV9 delivered bispecific nanobody attenuates amyloid burden in the gelsolin amyloidosis mouse model.

    abstract：:Gelsolin amyloidosis is a dominantly inherited, incurable type of amyloidosis. A single point mutation in the gelsolin gene (G654A is most common) results in the loss of a Ca2+  binding site in the second gelsolin domain. Consequently, this domain partly unfolds and exposes an otherwise buried furin cleavage site at t...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx056

    authors： Verhelle A,Nair N,Everaert I,Van Overbeke W,Supply L,Zwaenepoel O,Peleman C,Van Dorpe J,Lahoutte T,Devoogdt N,Derave W,Chuah MK,VandenDriessche T,Gettemans J

    更新日期：2017-04-01 00:00:00

  • Pathogenic mechanisms of tooth agenesis linked to paired domain mutations in human PAX9.

    abstract：:Mutations in the paired-domain transcription factor PAX9 are associated with non-syndromic tooth agenesis that preferentially affects posterior dentition. Of the 18 mutations identified to date, eight are phenotypically well-characterized missense mutations within the DNA-binding paired domain. We determined the struc...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddp221

    authors： Wang Y,Groppe JC,Wu J,Ogawa T,Mues G,D'Souza RN,Kapadia H

    更新日期：2009-08-01 00:00:00

  • Sequential cleavage of the proteins encoded by HNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, results in products acting in distinct cellular compartments.

    abstract：:This study provides first insights into the biosynthesis, structure, biochemistry and complex processing of the proteins encoded by hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID (NOT) and the yeast asparagine linked glycosylation 3 gene (ALG3), which encodes a mannosyltransferase. Unambiguous evi...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy315

    authors： Hacker B,Schultheiß C,Kurzik-Dumke U

    更新日期：2018-12-15 00:00:00

  • Sequence-specific stalling of DNA polymerase γ and the effects of mutations causing progressive ophthalmoplegia.

    abstract：:A large number of mutations in the gene encoding the catalytic subunit of mitochondrial DNA polymerase γ (POLγA) cause human disease. The Y955C mutation is common and leads to a dominant disease with progressive external ophthalmoplegia and other symptoms. The biochemical effect of the Y955C mutation has been extensiv...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq565

    authors： Atanassova N,Fusté JM,Wanrooij S,Macao B,Goffart S,Bäckström S,Farge G,Khvorostov I,Larsson NG,Spelbrink JN,Falkenberg M

    更新日期：2011-03-15 00:00:00

  • A conserved splicing mechanism of the LMNA gene controls premature aging.

    abstract：:Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder phenotypically characterized by many features of premature aging. Most cases of HGPS are due to a heterozygous silent mutation (c.1824C>T; p.Gly608Gly) that enhances the use of an internal 5' splice site (5'SS) in exon 11 of the LMNA pre-mRNA and l...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr385

    authors： Lopez-Mejia IC,Vautrot V,De Toledo M,Behm-Ansmant I,Bourgeois CF,Navarro CL,Osorio FG,Freije JM,Stévenin J,De Sandre-Giovannoli A,Lopez-Otin C,Lévy N,Branlant C,Tazi J

    更新日期：2011-12-01 00:00:00

  • The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract.

    abstract：:Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disease caused by the expansion of a polyglutamine tract within the SCA1 product, ataxin-1. Previously, using transgenic mice, it was demonstrated that in order for a mutant allele of ataxin-1 to cause disease it must be transported to the...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.1.25

    authors： Yue S,Serra HG,Zoghbi HY,Orr HT

    更新日期：2001-01-01 00:00:00

  • Thermosensory and mechanosensory perception in human genetic disease.

    abstract：:Peripheral sensory perception is established through an elaborate network of specialized neurons that mediate the translation of extraorganismal stimuli through the use of a broad array of receptors and downstream effector molecules. Studies of human genetic disorders, as well as mouse and other animal models, have id...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/ddp412

    authors： Tan PL,Katsanis N

    更新日期：2009-10-15 00:00:00

  • Overexpression of mutant superoxide dismutase 1 causes a motor axonopathy in the zebrafish.

    abstract：:The development of small animal models is of major interest to unravel the pathogenesis and treatment of neurodegenerative diseases, especially because of their potential in large-scale chemical and genetic screening. We have investigated the zebrafish as a model to study amyotrophic lateral sclerosis (ALS), a fatal n...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm193

    authors： Lemmens R,Van Hoecke A,Hersmus N,Geelen V,D'Hollander I,Thijs V,Van Den Bosch L,Carmeliet P,Robberecht W

    更新日期：2007-10-01 00:00:00

  • Neural cell recognition molecule L1: relating biological complexity to human disease mutations.

    abstract：:Human single gene disorders that affect the nervous system provide a host of natural mutations that can be deployed in the quest to understand its development and function. A paradigm for this approach is the study of disorders caused by mutations in the gene for the neural cell recognition molecule L1. L1 is the foun...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/9.6.879

    authors： Kenwrick S,Watkins A,De Angelis E

    更新日期：2000-04-12 00:00:00

  • Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation.

    abstract：:The widespread use of persistent organic polybrominated diphenyl ethers (PBDEs) as commercial flame retardants has raised concern about potential long-lived effects on human health. Epigenetic mechanisms, such as DNA methylation, are responsive to environmental influences and have long-lasting consequences. Autism spe...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds046

    authors： Woods R,Vallero RO,Golub MS,Suarez JK,Ta TA,Yasui DH,Chi LH,Kostyniak PJ,Pessah IN,Berman RF,LaSalle JM

    更新日期：2012-06-01 00:00:00

  • Relapsing diabetes can result from moderately activating mutations in KCNJ11.

    abstract：:Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensit...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi086

    authors： Gloyn AL,Reimann F,Girard C,Edghill EL,Proks P,Pearson ER,Temple IK,Mackay DJ,Shield JP,Freedenberg D,Noyes K,Ellard S,Ashcroft FM,Gribble FM,Hattersley AT

    更新日期：2005-04-01 00:00:00

  • Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas.

    abstract：:Meningiomas are common nervous system tumors, whose molecular pathogenesis is poorly understood. To date, the most frequent genetic alteration detected in these tumors is loss of heterozygosity (LOH) on chromosome 22q. This finding led to the identification of the neurofibromatosis 2 (NF2) tumor suppressor gene on 22q...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.10.1495

    authors： Gutmann DH,Donahoe J,Perry A,Lemke N,Gorse K,Kittiniyom K,Rempel SA,Gutierrez JA,Newsham IF

    更新日期：2000-06-12 00:00:00

  • The planar cell polarity gene Vangl2 is required for mammalian kidney-branching morphogenesis and glomerular maturation.

    abstract：:The planar cell polarity (PCP) pathway, incorporating non-canonical Wnt signalling, controls embryonic convergent (CE) extension, polarized cell division and ciliary orientation. It also limits diameters of differentiating renal tubules, with mutation of certain components of the pathway causing cystic kidneys. Mutati...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq397

    authors： Yates LL,Papakrivopoulou J,Long DA,Goggolidou P,Connolly JO,Woolf AS,Dean CH

    更新日期：2010-12-01 00:00:00

  • Tripolar chromosome segregation drives the association between maternal genotype at variants spanning PLK4 and aneuploidy in human preimplantation embryos.

    abstract：:Aneuploidy is prevalent in human embryos and is the leading cause of pregnancy loss. Many aneuploidies arise during oogenesis, increasing with maternal age. Superimposed on these meiotic aneuploidies are frequent errors occurring during early mitotic divisions, contributing to widespread chromosomal mosaicism. Here we...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy147

    authors： McCoy RC,Newnham LJ,Ottolini CS,Hoffmann ER,Chatzimeletiou K,Cornejo OE,Zhan Q,Zaninovic N,Rosenwaks Z,Petrov DA,Demko ZP,Sigurjonsson S,Handyside AH

    更新日期：2018-07-15 00:00:00

  • Suppression of peroxisomal membrane protein defects by peroxisomal ATP binding cassette (ABC) proteins.

    abstract：:X-Linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disorder characterized by reduced peroxisomal very long chain fatty acid (VLCFA) beta-oxidation. The X - ALD gene product (ALDP) is a peroxisomal transmembrane protein with an ATP binding cassette (ABC). ALDP and three other ABC proteins (PMP70, ALDR, P70R) ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/7.2.239

    authors： Braiterman LT,Zheng S,Watkins PA,Geraghty MT,Johnson G,McGuinness MC,Moser AB,Smith KD

    更新日期：1998-02-01 00:00:00

  • Common variation at 2q22.3 (ZEB2) influences the risk of renal cancer.

    abstract：:Genome-wide association studies (GWASs) of renal cell cancer (RCC) have identified four susceptibility loci thus far. To identify an additional RCC common susceptibility locus, we conducted a GWAS and performed a meta-analysis with published GWASs (totalling 2215 cases and 8566 controls of European background) and fol...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,meta分析

    doi：10.1093/hmg/dds489

    authors： Henrion M,Frampton M,Scelo G,Purdue M,Ye Y,Broderick P,Ritchie A,Kaplan R,Meade A,McKay J,Johansson M,Lathrop M,Larkin J,Rothman N,Wang Z,Chow WH,Stevens VL,Ryan Diver W,Gapstur SM,Albanes D,Virtamo J,Wu X,Bre

    更新日期：2013-02-15 00:00:00

  • Deletion size analysis of 1680 22q11.2DS subjects identifies a new recombination hotspot on chromosome 22q11.2.

    abstract：:Recurrent, de novo, meiotic non-allelic homologous recombination events between low copy repeats, termed LCR22s, leads to the 22q11.2 deletion syndrome (22q11.2DS; velo-cardio-facial syndrome/DiGeorge syndrome). Although most 22q11.2DS patients have a similar sized 3 million base pair (Mb), LCR22A-D deletion, some hav...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddy028

    authors： Guo T,Diacou A,Nomaru H,McDonald-McGinn DM,Hestand M,Demaerel W,Zhang L,Zhao Y,Ujueta F,Shan J,Montagna C,Zheng D,Crowley TB,Kushan-Wells L,Bearden CE,Kates WR,Gothelf D,Schneider M,Eliez S,Breckpot J,Swillen A,

    更新日期：2018-04-01 00:00:00

  • Collapsed methylation quantitative trait loci analysis for low frequency and rare variants.

    abstract：BACKGROUND:Single variant approaches have been successful in identifying DNA methylation quantitative trait loci (mQTL), although as with complex traits they lack the statistical power to identify the effects from rare genetic variants. We have undertaken extensive analyses to identify regions of low frequency and rare...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddw283

    authors： Richardson TG,Shihab HA,Hemani G,Zheng J,Hannon E,Mill J,Carnero-Montoro E,Bell JT,Lyttleton O,McArdle WL,Ring SM,Rodriguez S,Campbell C,Smith GD,Relton CL,Timpson NJ,Gaunt TR

    更新日期：2016-10-01 00:00:00