当前位置： SCI文献检索 > MOLECULAR GENETICS AND METABOLISM期刊下所有文献 > Next-generation sequencing of the monogenic obesity genes LEP, LEPR, MC4R, PCSK1 and POMC in a Norwegian cohort of patients with morbid obesity and normal weight controls.

Next-generation sequencing of the monogenic obesity genes LEP, LEPR, MC4R, PCSK1 and POMC in a Norwegian cohort of patients with morbid obesity and normal weight controls.

Abstract：

BACKGROUND:Rare sequence variants in at least five genes are known to cause monogenic obesity. In this study we aimed to investigate the prevalence of, and characterize, rare coding and splice site variants in LEP, LEPR, MC4R, PCSK1 and POMC in patients with morbid obesity and normal weight controls. METHOD:Targeted next-generation sequencing of all exons in LEP, LEPR, MC4R, PCSK1 and POMC was performed in 485 patients with morbid obesity and 327 normal weight population-based controls from Norway. RESULTS:In total 151 variants were detected. Twenty-eight (18.5%) of these were rare, coding or splice variants and five (3.3%) were novel. All individuals, except one control, were heterozygous for the 28 variants, and the distribution of the rare variants showed a significantly higher carrier frequency among cases than controls (9.9% vs. 4.9%, p=0.011). Four variants in MC4R were classified as pathogenic or likely pathogenic. CONCLUSION:Four cases (0.8%) of monogenic obesity were detected, all due to MC4R variants previously linked to monogenic obesity. Significant differences in carrier frequencies among patients with morbid obesity and normal weight controls suggest an association between heterozygous rare coding variants in these five genes and morbid obesity. However, additional studies in larger cohorts and functional testing of the novel variants identified are required to confirm the findings.

journal_name

Mol Genet Metab

journal_title

Molecular genetics and metabolism

authors

Nordang GBN,Busk ØL,Tveten K,Hanevik HI,Fell AKM,Hjelmesæth J,Holla ØL,Hertel JK

doi

10.1016/j.ymgme.2017.03.007

subject

Has Abstract

pub_date

2017-05-01 00:00:00

pages

51-56

issue

1

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(16)30831-9

journal_volume

121

pub_type

杂志文章

相关文献

MOLECULAR GENETICS AND METABOLISM文献大全
  • Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with acute liver failure following gastroenteritis.

    abstract：:We report a patient from a consanguineous family who presented with transient acute liver failure and biochemical patterns suggestive of disturbed urea cycle and mitochondrial function, for whom conventional genetic and metabolic investigations for acute liver failure failed to yield a diagnosis. Whole exome sequencin...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2016.03.001

    authors： Santra S,Cameron JM,Shyr C,Zhang L,Drögemöller B,Ross CJ,Wasserman WW,Wevers RA,Rodenburg RJ,Gupte G,Preece MA,van Karnebeek CD

    更新日期：2016-05-01 00:00:00

  • Slc19a2: cloning and characterization of the murine thiamin transporter cDNA and genomic sequence, the orthologue of the human TRMA gene.

    abstract：:Recently, our group and others cloned the TRMA disease gene, SLC19A2, which encodes a thiamin transporter. Here, we report the cloning and characterization of the full-length cDNA and genomic sequences of mouse Slc19a2. The Slc19a2 cDNA contained a 1494-bp open-reading frame, and had 5'- and 3'-untranslated regions of...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2001.3184

    authors： Oishi K,Hirai T,Gelb BD,Diaz GA

    更新日期：2001-06-01 00:00:00

  • Gaucher disease with parkinsonian manifestations: does glucocerebrosidase deficiency contribute to a vulnerability to parkinsonism?

    abstract：:Among the phenotypes associated with Gaucher disease, the deficiency of glucocerebrosidase, are rare patients with early onset, treatment-refractory parkinsonism. Sequencing of glucocerebrosidase in 17 such patients revealed 12 different genotypes. Fourteen patients had the common "non-neuronopathic" N370S mutation, i...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/s1096-7192(03)00071-4

    authors： Tayebi N,Walker J,Stubblefield B,Orvisky E,LaMarca ME,Wong K,Rosenbaum H,Schiffmann R,Bembi B,Sidransky E

    更新日期：2003-06-01 00:00:00

  • The mitochondrial 13513G>A mutation is associated with Leigh disease phenotypes independent of complex I deficiency in muscle.

    abstract：:The mitochondrial 13513G>A (D393N) mutation in the ND5 subunit of the respiratory chain complex I was initially described in association with MELAS syndrome. Recent observations have linked this mutation to Leigh disease. We screened for the 13513G>A mutation in a cohort of 265 patients with Leigh and Leigh-like disea...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2008.04.004

    authors： Brautbar A,Wang J,Abdenur JE,Chang RC,Thomas JA,Grebe TA,Lim C,Weng SW,Graham BH,Wong LJ

    更新日期：2008-08-01 00:00:00

  • Glucose tetrasaccharide as a biomarker for monitoring the therapeutic response to enzyme replacement therapy for Pompe disease.

    abstract：:A tetraglucose oligomer, Glcalpha1-6Glcalpha1-4Glcalpha1-4Glc, designated Glc4, has been shown to be a putative biomarker for the diagnosis of Pompe disease. The purpose of this study was to assess whether Glc4 could be used to monitor the therapeutic response to recombinant human acid alpha glucosidase (rhGAA) enzyme...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2005.03.010

    authors： An Y,Young SP,Kishnani PS,Millington DS,Amalfitano A,Corz D,Chen YT

    更新日期：2005-08-01 00:00:00

  • SERCA1 protein expression in muscle of patients with Brody disease and Brody syndrome and in cultured human muscle fibers.

    abstract：:Brody disease is an inherited myopathy associated with a defective function of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 1 (SERCA1) protein. Mutations in the ATP2A1 gene have been reported only in some patients. Therefore it has been proposed to distinguish patients with ATP2A1 mutations, Brody disease (BD), fr...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2013.07.015

    authors： Guglielmi V,Vattemi G,Gualandi F,Voermans NC,Marini M,Scotton C,Pegoraro E,Oosterhof A,Kósa M,Zádor E,Valente EM,De Grandis D,Neri M,Codemo V,Novelli A,van Kuppevelt TH,Dallapiccola B,van Engelen BG,Ferlini A,Tomell

    更新日期：2013-09-01 00:00:00

  • Propionyl-CoA carboxylase - A review.

    abstract：:Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB to form a hetero-dodecamer. Dysfunction of PCC leads to the inherited metabolic disorder propionic acidemia, which can result in an affected individual present...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1016/j.ymgme.2017.10.002

    authors： Wongkittichote P,Ah Mew N,Chapman KA

    更新日期：2017-12-01 00:00:00

  • Regulation and tissue-specific expression of δ-aminolevulinic acid synthases in non-syndromic sideroblastic anemias and porphyrias.

    abstract：:Recently, new genes and molecular mechanisms have been identified in patients with porphyrias and sideroblastic anemias (SA). They all modulate either directly or indirectly the δ-aminolevulinic acid synthase (ALAS) activity. ALAS, is encoded by two genes: the erythroid-specific (ALAS2), and the ubiquitously expressed...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1016/j.ymgme.2019.01.015

    authors： Peoc'h K,Nicolas G,Schmitt C,Mirmiran A,Daher R,Lefebvre T,Gouya L,Karim Z,Puy H

    更新日期：2019-11-01 00:00:00

  • Overexpression of human antiquitin in E. coli: enzymatic characterization of twelve ALDH7A1 missense mutations associated with pyridoxine-dependent epilepsy.

    abstract：:Pyridoxine dependent epilepsy is an autosomal recessive disorder characterized by early onset seizures responsive to pyridoxine and caused by a defect in the α-aminoadipic semialdehyde dehydrogenase (antiquitin) gene (ALDH7A1). In order to characterize the effects of a series of twelve disease-associated ALDH7A1 misse...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2012.06.008

    authors： Coulter-Mackie MB,Li A,Lian Q,Struys E,Stockler S,Waters PJ

    更新日期：2012-08-01 00:00:00

  • Molecular genetic, biochemical, and clinical implications of gonadotropin receptor mutations.

    abstract：:Human reproductive function is regulated mainly by luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Mutations of the human LH/ chorionic gonadotropin receptor (LHR) and the FSH receptor (FSHR) leading to either constitutive activation or inactivation of the receptors have been identified. All activatin...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.1997.2650

    authors： Chan WY

    更新日期：1998-02-01 00:00:00

  • Molecular analysis of the UROD gene in 17 Argentinean patients with familial porphyria cutanea tarda: characterization of four novel mutations.

    abstract：:Porphyria cutanea tarda (PCT) is caused by decreased activity of uroporphyrinogen decarboxylase (UROD) in the liver. The disease usually occurs in adulthood and is characterized by cutaneous photosensitivity, hyperpigmentation, skin fragility and hypertrichosis, due to the accumulation of porphyrins produced by oxidat...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2012.02.002

    authors： Méndez M,Rossetti MV,Gómez-Abecia S,Morán-Jiménez MJ,Parera V,Batlle A,Enríquez de Salamanca R

    更新日期：2012-04-01 00:00:00

  • Combined alpha-delta platelet storage pool deficiency is associated with mutations in GFI1B.

    abstract：:Combined alpha-delta platelet storage pool deficiency is characterized by the absence or reduction in the number of both alpha granules and dense bodies. This disorder can have variable severity as well as a variable inheritance pattern. We describe two patients from unrelated families with combined alpha-delta storag...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2016.12.006

    authors： Ferreira CR,Chen D,Abraham SM,Adams DR,Simon KL,Malicdan MC,Markello TC,Gunay-Aygun M,Gahl WA

    更新日期：2017-03-01 00:00:00

  • Late-onset Pompe disease (LOPD): correlations between respiratory muscles CT and MRI features and pulmonary function.

    abstract：:Late onset Pompe disease (LOPD) is a rare muscle disorder often characterized, along the disease course, by severe respiratory failure. We describe herein respiratory muscles and lung abnormalities in LOPD patients using MR imaging and CT examinations correlated to pulmonary function tests. Ten LOPD patients were stud...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2013.06.023

    authors： Gaeta M,Barca E,Ruggeri P,Minutoli F,Rodolico C,Mazziotti S,Milardi D,Musumeci O,Toscano A

    更新日期：2013-11-01 00:00:00

  • TRMU deficiency: A broad clinical spectrum responsive to cysteine supplementation.

    abstract：:TRMU is a nuclear gene crucial for mitochondrial DNA translation by encoding tRNA 5-methylaminomethyl-2-thiouridylate methyltransferase, which thiolates mitochondrial tRNA. Biallelic pathogenic variants in TRMU are associated with transient infantile liver failure. Other less common presentations such as Leigh syndrom...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2021.01.005

    authors： Murali CN,Soler-Alfonso C,Loomes KM,Shah AA,Monteil D,Padilla CD,Scaglia F,Ganetzky R

    更新日期：2021-01-14 00:00:00

  • Functional analysis of mutations in the glucose-6-phosphate transporter that cause glycogen storage disease type Ib.

    abstract：:The glucose-6-phosphate transporter (G6PT) deficient in glycogen storage disease type Ib is a phosphate (P(i))-linked antiporter capable of G6P: P(i) and P(i):P(i) exchanges. We previously characterized G6PT mutations by measuring G6P uptake activities in microsomes co-expressing G6PT and glucose-6-phosphatase-alpha. ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2008.08.005

    authors： Chen SY,Pan CJ,Lee S,Peng W,Chou JY

    更新日期：2008-12-01 00:00:00

  • Impact of premature birth and critical illness on neonatal range of plasma amino acid concentrations determined by LC-MS/MS.

    abstract：BACKGROUND:The number of newborns and the number of disorders detected by large-scale screening programs has increased dramatically in the last decade. Newborn screening is a multi-step process requiring confirmatory testing to establish and refine a diagnosis. Whereas screening cutoffs are established to detect all ca...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2011.08.020

    authors： Oladipo OO,Weindel AL,Saunders AN,Dietzen DJ

    更新日期：2011-12-01 00:00:00

  • Pilot study of newborn screening for six lysosomal storage diseases using Tandem Mass Spectrometry.

    abstract：BACKGROUND:There is current expansion of newborn screening (NBS) programs to include lysosomal storage disorders because of the availability of treatments that produce an optimal clinical outcome when started early in life. OBJECTIVE:To evaluate the performance of a multiplex-tandem mass spectrometry (MS/MS) enzymatic...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2016.05.015

    authors： Elliott S,Buroker N,Cournoyer JJ,Potier AM,Trometer JD,Elbin C,Schermer MJ,Kantola J,Boyce A,Turecek F,Gelb MH,Scott CR

    更新日期：2016-08-01 00:00:00

  • Methods of diagnosis of patients with Pompe disease: Data from the Pompe Registry.

    abstract：:Pompe disease is a rare, autosomal recessive disorder characterized by deficiency of lysosomal acid alpha-glucosidase and accumulation of lysosomal glycogen in many tissues. The variable clinical manifestations, broad phenotypic spectrum, and overlap of signs and symptoms with other neuromuscular diseases make diagnos...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2014.07.014

    authors： Kishnani PS,Amartino HM,Lindberg C,Miller TM,Wilson A,Keutzer J

    更新日期：2014-09-01 00:00:00

  • A new diagnostic assay for glycogen storage disease type II in mixed leukocytes.

    abstract：:We have established a new method for the enzymatic diagnosis of glycogen storage disease type II (Pompe disease or acid maltase deficiency) using mixed leukocytes. The method employs glycogen and 4-methylumbelliferyl-alpha-D-glucopyranoside (4MU-alphaGlc) as substrates for measuring the lysosomal acid alpha-glucosidas...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2005.10.016

    authors： Okumiya T,Keulemans JL,Kroos MA,Van der Beek NM,Boer MA,Takeuchi H,Van Diggelen OP,Reuser AJ

    更新日期：2006-05-01 00:00:00

  • Trans-generational exposure to low levels of rhodamine B does not adversely affect litter size or liver function in murine mucopolysaccharidosis type IIIA.

    abstract：:MPS IIIA is a lysosomal storage disorder caused by mutations in the sulphamidase gene, resulting in the accumulation of heparan sulphate glycosaminoglycans (HS GAGs). Symptoms predominantly manifest in the CNS and there is no current therapy that effectively addresses neuropathology in MPS IIIA patients. Recent studie...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2010.06.008

    authors： Roberts AL,Fletcher JM,Moore L,Byers S

    更新日期：2010-10-01 00:00:00

  • Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects.

    abstract：:Oxidative metabolism of glucose is regulated by pyruvate dehydrogenase (PDH) that can be inhibited by isoforms of PDH kinase (PDK). Recently, increased PDK activity has been implicated in the pathogenesis of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) in obese subjects. Using quantitative RT...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.1998.2748

    authors： Majer M,Popov KM,Harris RA,Bogardus C,Prochazka M

    更新日期：1998-10-01 00:00:00

  • Next generation sequencing in research and diagnostics of ocular birth defects.

    abstract：:Sequence capture enrichment (SCE) strategies and massively parallel next generation sequencing (NGS) are expected to increase the rate of gene discovery for genetically heterogeneous hereditary diseases, but at present, there are very few examples of successful application of these technologic advances in translationa...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2010.03.004

    authors： Raca G,Jackson C,Warman B,Bair T,Schimmenti LA

    更新日期：2010-06-01 00:00:00

  • Pyrimethamine increases β-hexosaminidase A activity in patients with Late Onset Tay Sachs.

    abstract：OBJECTIVE:To assess whether or not pyrimethamine (PMT) can be used to enhance β-hexosaminidase A activity (HexA) in subjects with Late Onset Tay Sachs (LOTS), we studied the effect of incremental doses of PMT in vivo in 9 LOTS patients carrying the αG269S/c.1278insTACT mutations. METHODS:PMT treatment was initiated at...

    journal_title：Molecular genetics and metabolism

    pub_type： 临床试验,杂志文章

    doi：10.1016/j.ymgme.2010.11.163

    authors： Osher E,Fattal-Valevski A,Sagie L,Urshanski N,Amir-Levi Y,Katzburg S,Peleg L,Lerman-Sagie T,Zimran A,Elstein D,Navon R,Stern N,Valevski A

    更新日期：2011-03-01 00:00:00

  • Carrier frequency of the Bloom syndrome blmAsh mutation in the Ashkenazi Jewish population.

    abstract：:Bloom syndrome is more common in individuals of Ashkenazi Jewish descent than in any other population, and one particular mutation in the Bloom syndrome gene, blmAsh, is homozygous in nearly all Ashkenazi Jewish persons with Bloom syndrome. We have determined the frequency of blmAsh in 1491 Ashkenazi Jewish persons wi...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.1998.2733

    authors： Li L,Eng C,Desnick RJ,German J,Ellis NA

    更新日期：1998-08-01 00:00:00

  • Use of TaqI digestion may lead to incorrect molecular diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

    abstract：:Congenital adrenal hyperplasia (CAH) is a common autosomal recessive disorder mainly caused by defects in the steroid 21-hydroxylase (CYP21) gene. For reliable and accurate mutation detection in the CYP21 gene it is important to separate the CYP21 gene from the highly homologous CYP21P pseudogene. For this, several di...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2000.3023

    authors： Lee HH,de Wijs IJ,Sistermans EA

    更新日期：2000-08-01 00:00:00

  • Molecular screening of the human glutamine-fructose-6-phosphate amidotransferase 1 (GFPT1) gene and association studies with diabetes and diabetic nephropathy.

    abstract：:Increased glucose metabolism through the hexosamine pathway may result in insulin resistance, impaired insulin secretion, and diabetic nephropathy. We hypothesized that variants of GFPT1 encoding glutamine-fructose-6-phosphate amidotransferase, the rate limiting enzyme in this pathway, could increase GFPT1 gene expres...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2004.05.004

    authors： Elbein SC,Zheng H,Jia Y,Chu W,Cooper JJ,Hale T,Zhang Z

    更新日期：2004-08-01 00:00:00

  • Uncovering microdeletions in patients with severe Glut-1 deficiency syndrome using SNP oligonucleotide microarray analysis.

    abstract：:Glut-1 facilitates the diffusion of glucose across the blood-brain barrier and is responsible for glucose entry into the brain. Impaired glucose transport across the blood-brain barrier results in Glut-1 deficiency syndrome (Glut-1 DS, OMIM 606777), characterized in its most severe form by infantile seizures, developm...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2010.03.007

    authors： Levy B,Wang D,Ullner PM,Engelstad K,Yang H,Nahum O,Chung WK,De Vivo DC

    更新日期：2010-06-01 00:00:00

  • Intracellular galactose-1-phosphate accumulation leads to environmental stress response in yeast model.

    abstract：:In humans, deficiency of galactose-1-phosphate uridyltransferase (GALT) can lead a metabolic disorder Classic Galactosemia. Although the biochemical abnormalities associated with this disease have been described in detail, few attempts have been made to characterize the pathogenic mechanisms of this disorder at the mo...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2005.08.002

    authors： Slepak T,Tang M,Addo F,Lai K

    更新日期：2005-11-01 00:00:00

  • Approach to gene therapy of glycogenosis type II (Pompe disease).

    abstract：:Pompe disease is a generalized lysosomal glycogenosis affecting essentially the skeletal muscles and the heart. It is due to the deficiency of acid alpha-glucosidase, also called acid maltase, involved in glycogen degradation by the cleavage of alpha-1,4 and alpha-1,6 glycosidic linkages. The severe infantile, milder ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.2000.3003

    authors： Poenaru L

    更新日期：2000-07-01 00:00:00

  • Early neonatal diagnosis of long-chain 3-hydroxyacyl coenzyme a dehydrogenase and mitochondrial trifunctional protein deficiencies.

    abstract：:Tandem mass spectrometry (MS/MS) has been introduced in several newborn screening programs for the detection of a large number of inborn errors of metabolism, including fatty acid oxidation disorders (FAOD). Early identification and treatment of FAOD have the potential to improve outcome and may be life-saving in some...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2001.3282

    authors： Hintz SR,Matern D,Strauss A,Bennett MJ,Hoyme HE,Schelley S,Kobori J,Colby C,Lehman NL,Enns GM

    更新日期：2002-02-01 00:00:00