Homozygous hereditary coproporphyria caused by an arginine to tryptophane substitution in coproporphyrinogen oxidase and common intragenic polymorphisms.

Abstract:

:Coproporphyrinogen oxidase is a mitochondrial heme-biosynthetic enzyme that converts coproporphyrinogen to protoporphyrinogen. Inherited deficiency of this enzyme causes the human genetic disease hereditary coproporphyria. Recently, we isolated, sequenced and expressed the cDNA encoding human coproporphyrinogen oxidase. This allowed us to investigate the nature of the defect leading to a profound deficiency of coproporphyrinogen oxidase in a patient with homozygous hereditary coproporphyria. Using reverse-transcription, amplification of the cDNA and direct sequencing of the amplified products, we found a point mutation resulted in an arginine to tryptophane substitution (R231W). Expression studies of normal and mutated cDNAs in a bacterial system demonstrated that this substitution resulted in the synthesis of an unstable protein with a residual catalytic activity. This is the first mutation to be found at the coproporphyrinogen oxidase locus. Furthermore, three common polymorphisms within the coproporphyrinogen oxidase gene were detected. Two DNA polymorphisms resulted in amino acids changes (H172N and V194I) and the third one was silent (E230E).

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Martasek P,Nordmann Y,Grandchamp B

doi

10.1093/hmg/3.3.477

subject

Has Abstract

pub_date

1994-03-01 00:00:00

pages

477-80

issue

3

eissn

0964-6906

issn

1460-2083

journal_volume

3

pub_type

杂志文章
  • Cellular stressors may alter islet hormone cell proportions by moderation of alternative splicing patterns.

    abstract::Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddz094

    authors: Jeffery N,Richardson S,Chambers D,Morgan NG,Harries LW

    更新日期:2019-08-15 00:00:00

  • A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene.

    abstract::The identification of mouse models for the various forms of human neurosensory non-syndromic recessive deafness would constitute a major advance in the study of human deafness. Here we describe the localization of a human gene for neurosensory, nonsyndromic recessive deafness (NSRD2) to chromosome 11q13.5 by linkage a...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/3.6.989

    authors: Guilford P,Ayadi H,Blanchard S,Chaib H,Le Paslier D,Weissenbach J,Drira M,Petit C

    更新日期:1994-06-01 00:00:00

  • Selective inhibition of caspases in skeletal muscle reverses the apoptotic synaptic degeneration in slow-channel myasthenic syndrome.

    abstract::Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca(2+) overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgen...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddt397

    authors: Zhu H,Pytel P,Gomez CM

    更新日期:2014-01-01 00:00:00

  • A whole-blood transcriptome meta-analysis identifies gene expression signatures of cigarette smoking.

    abstract::Cigarette smoking is a leading modifiable cause of death worldwide. We hypothesized that cigarette smoking induces extensive transcriptomic changes that lead to target-organ damage and smoking-related diseases. We performed a meta-analysis of transcriptome-wide gene expression using whole blood-derived RNA from 10,233...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,meta分析

    doi:10.1093/hmg/ddw288

    authors: Huan T,Joehanes R,Schurmann C,Schramm K,Pilling LC,Peters MJ,Mägi R,DeMeo D,O'Connor GT,Ferrucci L,Teumer A,Homuth G,Biffar R,Völker U,Herder C,Waldenberger M,Peters A,Zeilinger S,Metspalu A,Hofman A,Uitterlinden

    更新日期:2016-11-01 00:00:00

  • Widespread enzymatic correction of CNS tissues by a single intracerebral injection of therapeutic lentiviral vector in leukodystrophy mouse models.

    abstract::Leukodystrophies are rare diseases caused by defects in the genes coding for lysosomal enzymes that degrade several glycosphingolipids. Gene therapy for leukodystrophies requires efficient distribution of the missing enzymes in CNS tissues to prevent demyelination and neurodegeneration. In this work, we targeted the e...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddq099

    authors: Lattanzi A,Neri M,Maderna C,di Girolamo I,Martino S,Orlacchio A,Amendola M,Naldini L,Gritti A

    更新日期:2010-06-01 00:00:00

  • From enhanceropathies to the epigenetic manifold underlying human cognition.

    abstract::A vast portion of intellectual disability and autism spectrum disorders is genetically caused by mutations in chromatin modulators. These proteins play key roles in development and are also highly expressed in the adult brain. Specifically, the pivotal role of chromatin regulation in transcription has placed enhancers...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审

    doi:10.1093/hmg/ddz196

    authors: Vitriolo A,Gabriele M,Testa G

    更新日期:2019-11-21 00:00:00

  • Pax2 gene dosage influences cystogenesis in autosomal dominant polycystic kidney disease.

    abstract::Mutations in PKD1 cause dominant polycystic kidney disease (PKD), characterized by large fluid-filled kidney cysts in adult life, but the molecular mechanism of cystogenesis remains obscure. Ostrom et al. [Dev. Biol., 219, 250-258 (2000)] showed that reduced dosage of Pax2 caused increased apoptosis, and ameliorated c...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl428

    authors: Stayner C,Iglesias DM,Goodyer PR,Ellis L,Germino G,Zhou J,Eccles MR

    更新日期:2006-12-15 00:00:00

  • High resolution time-course mapping of early transcriptomic, molecular and cellular phenotypes in Huntington's disease CAG knock-in mice across multiple genetic backgrounds.

    abstract::Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in underst...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddx006

    authors: Ament SA,Pearl JR,Grindeland A,St Claire J,Earls JC,Kovalenko M,Gillis T,Mysore J,Gusella JF,Lee JM,Kwak S,Howland D,Lee MY,Baxter D,Scherler K,Wang K,Geman D,Carroll JB,MacDonald ME,Carlson G,Wheeler VC,Price N

    更新日期:2017-03-01 00:00:00

  • HDAC inhibitors rescue multiple disease-causing CFTR variants.

    abstract::Understanding the role of the epigenome in protein-misfolding diseases remains a challenge in light of genetic diversity found in the world-wide population revealed by human genome sequencing efforts and the highly variable response of the disease population to therapeutics. An ever-growing body of evidence has shown ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddz026

    authors: Anglès F,Hutt DM,Balch WE

    更新日期:2019-06-15 00:00:00

  • Deletion of long-range sequences at Sox10 compromises developmental expression in a mouse model of Waardenburg-Shah (WS4) syndrome.

    abstract::The transcription factor SOX10 is mutated in the human neurocristopathy Waardenburg-Shah syndrome (WS4), which is characterized by enteric aganglionosis and pigmentation defects. SOX10 directly regulates genes expressed in neural crest lineages, including the enteric ganglia and melanocytes. Although some SOX10 target...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddi442

    authors: Antonellis A,Bennett WR,Menheniott TR,Prasad AB,Lee-Lin SQ,NISC Comparative Sequencing Program.,Green ED,Paisley D,Kelsh RN,Pavan WJ,Ward A

    更新日期:2006-01-15 00:00:00

  • Mouse models of X-linked juvenile retinoschisis have an early onset phenotype, the severity of which varies with genotype.

    abstract::X-linked juvenile retinoschisis (XLRS) is an early-onset inherited condition that affects primarily males and is characterized by cystic lesions of the inner retina, decreased visual acuity and contrast sensitivity and a selective reduction of the electroretinogram (ERG) b-wave. Although XLRS is genetically heterogene...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddz122

    authors: Liu Y,Kinoshita J,Ivanova E,Sun D,Li H,Liao T,Cao J,Bell BA,Wang JM,Tang Y,Brydges S,Peachey NS,Sagdullaev BT,Romano C

    更新日期:2019-09-15 00:00:00

  • Generalized metabolic bone disease and fracture risk in Rothmund-Thomson syndrome.

    abstract::Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone diseas...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddx178

    authors: Cao F,Lu L,Abrams SA,Hawthorne KM,Tam A,Jin W,Dawson B,Shypailo R,Liu H,Lee B,Nagamani SCS,Wang LL

    更新日期:2017-08-15 00:00:00

  • miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo.

    abstract::Alzheimer's disease (AD) and related tauopathies comprise a large group of neurodegenerative diseases associated with the pathological aggregation of tau protein. While much effort has focused on understanding the function of tau, little is known about the endogenous mechanisms regulating tau metabolism in vivo and ho...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddv377

    authors: Smith PY,Hernandez-Rapp J,Jolivette F,Lecours C,Bisht K,Goupil C,Dorval V,Parsi S,Morin F,Planel E,Bennett DA,Fernandez-Gomez FJ,Sergeant N,Buée L,Tremblay MÈ,Calon F,Hébert SS

    更新日期:2015-12-01 00:00:00

  • Over-expression of alpha-synuclein in human neural progenitors leads to specific changes in fate and differentiation.

    abstract::Missense mutations and extra copies of the alpha-Synuclein gene result in Parkinson disease (PD). Human stem and progenitor cells can be expanded from embryonic tissues and provide a source of non-transformed neural cells to explore the effects of these pathogenic mutations specifically in human nervous tissue. We ove...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddm008

    authors: Schneider BL,Seehus CR,Capowski EE,Aebischer P,Zhang SC,Svendsen CN

    更新日期:2007-03-15 00:00:00

  • Alzheimer-associated C allele of the promoter polymorphism -22C>T causes a critical neuron-specific decrease of presenilin 1 expression.

    abstract::We, amongst others, have shown that CC homozygosity at the -22C>T promoter polymorphism in presenilin 1 (PSEN1) is associated with increased risk for Alzheimer's disease (AD). Also, studies in AD brains suggested that CC homozygosity increased the risk for AD by increasing the Abeta load. We characterized the PSEN1 pr...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddg098

    authors: Theuns J,Remacle J,Killick R,Corsmit E,Vennekens K,Huylebroeck D,Cruts M,Van Broeckhoven C

    更新日期:2003-04-15 00:00:00

  • The fundamental and medical impacts of recent progress in research on hereditary hearing loss.

    abstract::What would define real progress in the field of deafness research in fundamental and medical terms? In fundamental terms, progress would be measured by an improvement in our knowledge of the development and physiology of the ear. In medical terms, progress would lead to the division of the broad category of hearing de...

    journal_title:Human molecular genetics

    pub_type: 杂志文章,评审

    doi:10.1093/hmg/7.10.1589

    authors: Kalatzis V,Petit C

    更新日期:1998-01-01 00:00:00

  • Inhibition of GSK3β improves hippocampus-dependent learning and rescues neurogenesis in a mouse model of fragile X syndrome.

    abstract::Fragile X syndrome (FXS), a common inherited form of intellectual disability with learning deficits, results from a loss of fragile X mental retardation protein (FMRP). Despite extensive research, treatment options for FXS remain limited. Since FMRP is known to play an important role in adult hippocampal neurogenesis ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr501

    authors: Guo W,Murthy AC,Zhang L,Johnson EB,Schaller EG,Allan AM,Zhao X

    更新日期:2012-02-01 00:00:00

  • The utrophin A 5'-UTR drives cap-independent translation exclusively in skeletal muscles of transgenic mice and interacts with eEF1A2.

    abstract::The molecular mechanisms regulating expression of utrophin A are of therapeutic interest since upregulating its expression at the sarcolemma can compensate for the lack of dystrophin in animal models of Duchenne Muscular Dystrophy (DMD). The 5'-UTR of utrophin A has been previously shown to drive cap-independent inter...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddp591

    authors: Miura P,Coriati A,Bélanger G,De Repentigny Y,Lee J,Kothary R,Holcik M,Jasmin BJ

    更新日期:2010-04-01 00:00:00

  • The conserved translocase Tim17 prevents mitochondrial DNA loss.

    abstract::Maintenance of an intact mitochondrial genome is essential for oxidative phosphorylation in all eukaryotes. Depletion of mitochondrial genome copy number can have severe pathological consequences due to loss of respiratory capacity. In Saccharomyces cerevisiae, several bifunctional metabolic enzymes have been shown to...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddn313

    authors: Iacovino M,Granycome C,Sembongi H,Bokori-Brown M,Butow RA,Holt IJ,Bateman JM

    更新日期:2009-01-01 00:00:00

  • Huntingtin affinity for partners is not changed by polyglutamine length: aggregation itself triggers aberrant interactions.

    abstract::Huntington's disease (HD) is caused by the expansion mutation above a length threshold of a polyglutamine (polyQ) stretch in the huntingtin (Htt) protein. Mutant Htt (mHtt) pathogenicity is proposed to rely on its malfunction and propensity to misfold and aggregate. Htt has scaffolding properties and has been reported...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddr178

    authors: Davranche A,Aviolat H,Zeder-Lutz G,Busso D,Altschuh D,Trottier Y,Klein FA

    更新日期:2011-07-15 00:00:00

  • Genetic control of serum IgE levels and asthma: linkage and linkage disequilibrium studies in an isolated population.

    abstract::Immunoglobulin E (IgE) concentration in serum is elevated in atopic diseases such as asthma. A large genomic region on chromosome 5 has previously been implicated in the control of IgE levels and bronchial hyperreactivity and may, therefore, harbor genes predisposing to asthma. In an effort to confirm this linkage and...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/6.12.2069

    authors: Laitinen T,Kauppi P,Ignatius J,Ruotsalainen T,Daly MJ,Kääriäinen H,Kruglyak L,Laitinen H,de la Chapelle A,Lander ES,Laitinen LA,Kere J

    更新日期:1997-11-01 00:00:00

  • The HLA class III subregion is responsible for an increased breast cancer risk.

    abstract::BRCA1 and BRCA2 germline mutations account for <5% of breast cancer cases. Less penetrant breast cancer susceptibility genes are likely to exist. Earlier studies have suggested involvement of the HLA region. The HLA region was genotyped with 24 microsatellite markers and markers for two single nucleotide polymorphisms...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddg245

    authors: de Jong MM,Nolte IM,de Vries EG,Schaapveld M,Kleibeuker JH,Oosterom E,Oosterwijk JC,van der Hout AH,van der Steege G,Bruinenberg M,Boezen HM,Te Meerman GJ,van der Graaf WT

    更新日期:2003-09-15 00:00:00

  • Neuropeptide S and G protein-coupled receptor 154 modulate macrophage immune responses.

    abstract::G protein-coupled receptor 154 (GPR154) is a recently discovered asthma susceptibility gene upregulated in the airways of asthma patients. We previously observed increased pulmonary mRNA expression of the murine ortholog Gpr154 in a mouse model of ovalbumin (OVA)-induced inflammation. However, the expression profile o...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl090

    authors: Pulkkinen V,Majuri ML,Wang G,Holopainen P,Obase Y,Vendelin J,Wolff H,Rytilä P,Laitinen LA,Haahtela T,Laitinen T,Alenius H,Kere J,Rehn M

    更新日期:2006-05-15 00:00:00

  • Regulation of murine survival motor neuron (Smn) protein levels by modifying Smn exon 7 splicing.

    abstract::Proximal spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron gene (SMN1). In humans, two nearly identical copies of SMN exist and differ only by a single non-polymorphic C-->T nucleotide transition in exon 7. SMN1 contains a 'C' nucleotide at the +6 position of exon 7 and produces primari...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/10.23.2727

    authors: DiDonato CJ,Lorson CL,De Repentigny Y,Simard L,Chartrand C,Androphy EJ,Kothary R

    更新日期:2001-11-01 00:00:00

  • Molecular disturbance underlies to arrhythmogenic cardiomyopathy induced by transgene content, age and exercise in a truncated PKP2 mouse model.

    abstract::Arrhythmogenic cardiomyopathy (ACM) is a disorder characterized by a progressive ventricular myocardial replacement by fat and fibrosis, which lead to ventricular arrhythmias and sudden cardiac death. Mutations in the desmosomal gene Plakophilin-2 (PKP2) accounts for >40% of all known mutations, generally causing a tr...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddw213

    authors: Moncayo-Arlandi J,Guasch E,Sanz-de la Garza M,Casado M,Garcia NA,Mont L,Sitges M,Knöll R,Buyandelger B,Campuzano O,Diez-Juan A,Brugada R

    更新日期:2016-09-01 00:00:00

  • Mitochondrial ATP synthase deficiency due to a mutation in the ATP5E gene for the F1 epsilon subunit.

    abstract::F1Fo-ATP synthase is a key enzyme of mitochondrial energy provision producing most of cellular ATP. So far, mitochondrial diseases caused by isolated disorders of the ATP synthase have been shown to result from mutations in mtDNA genes for the subunits ATP6 and ATP8 or in nuclear genes encoding the biogenesis factors ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddq254

    authors: Mayr JA,Havlícková V,Zimmermann F,Magler I,Kaplanová V,Jesina P,Pecinová A,Nusková H,Koch J,Sperl W,Houstek J

    更新日期:2010-09-01 00:00:00

  • A human keratin 10 knockout causes recessive epidermolytic hyperkeratosis.

    abstract::Epidermolytic hyperkeratosis (EHK) is a blistering skin disease inherited as an autosomal-dominant trait. The disease is caused by genetic defects of the epidermal keratin K1 or K10, leading to an impaired tonofilament network of differentiating epidermal cells. Here, we describe for the first time a kindred with rece...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddl028

    authors: Müller FB,Huber M,Kinaciyan T,Hausser I,Schaffrath C,Krieg T,Hohl D,Korge BP,Arin MJ

    更新日期:2006-04-01 00:00:00

  • Paternal monoallelic expression of PEG3 in the human placenta.

    abstract::Genomic imprinting is the phenomenon whereby mono-allelic expression of certain genes occurs depending on their parental origin. The observation that imprinting only occurs in placental mammals has led to the suggestion that it may play a role in this form of reproduction. In the present study we have investigated the...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/10.10.1093

    authors: Hiby SE,Lough M,Keverne EB,Surani MA,Loke YW,King A

    更新日期:2001-05-01 00:00:00

  • Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease.

    abstract::Sphingosine-1-phosphate (S1P) is a lipid-signaling molecule produced by sphingosine kinase in response to a wide number of stimuli. By acting through a family of widely expressed G protein-coupled receptors, S1P regulates diverse physiological processes. Here we examined the role of S1P signaling in neurodegeneration ...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddn126

    authors: Wu YP,Mizugishi K,Bektas M,Sandhoff R,Proia RL

    更新日期:2008-08-01 00:00:00

  • Whole-exome imputation of sequence variants identified two novel alleles associated with adult body height in African Americans.

    abstract::Adult body height is a quantitative trait for which genome-wide association studies (GWAS) have identified numerous loci, primarily in European populations. These loci, comprising common variants, explain <10% of the phenotypic variance in height. We searched for novel associations between height and common (minor all...

    journal_title:Human molecular genetics

    pub_type: 杂志文章

    doi:10.1093/hmg/ddu361

    authors: Du M,Auer PL,Jiao S,Haessler J,Altshuler D,Boerwinkle E,Carlson CS,Carty CL,Chen YD,Curtis K,Franceschini N,Hsu L,Jackson R,Lange LA,Lettre G,Monda KL,National Heart, Lung, and Blood Institute (NHLBI) GO Exome Sequencing

    更新日期:2014-12-15 00:00:00