当前位置： SCI文献检索 > MOLECULAR GENETICS AND METABOLISM期刊下所有文献 > Clinical research for rare disease: opportunities, challenges, and solutions.

Clinical research for rare disease: opportunities, challenges, and solutions.

Abstract：

:Over 7000 rare diseases, each <200,000 US residents, affect nearly 30 million people in the United States. Furthermore, for the 10% of people with a rare disease and for their families, these disorders no longer seem rare. Molecular genetics have characterized the cause of many rare diseases and provide unprecedented opportunities for identifying patients, determining phenotypes, and devising treatments to prevent, stabilize, or improve each disease. Rare disease research poses challenges to investigators requiring specific approaches to: (1) the design of clinical studies; (2) the funding of research programs; (3) the discovery, testing, and approval of new treatments, and (4) the training of clinical scientists. Rigorous, statistically-valid, natural history-controlled, cross-over, and n-of-1 trials can establish efficacy and support regulatory approval of new treatments for rare diseases. The U.S. Orphan Drug Act of the U.S. FDA has stimulated industry investment in clinical trials to develop treatments for rare diseases. For trainees interested in finding a treatment for a rare disease, a commitment to longitudinal care of patients provides a base for the characterization of phenotype and natural history, a stimulus for innovation, a target population for research and helps fund training and research. The scientific methodology, financial resources, and logistics of clinical research for rare diseases have changed dramatically in the past two decades resulting in increased understanding of the pathophysiology of these disorders and direct benefit to patients.

journal_name

Mol Genet Metab

journal_title

Molecular genetics and metabolism

authors

Griggs RC,Batshaw M,Dunkle M,Gopal-Srivastava R,Kaye E,Krischer J,Nguyen T,Paulus K,Merkel PA,Rare Diseases Clinical Research Network.

doi

10.1016/j.ymgme.2008.10.003

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

20-6

issue

1

eissn

1096-7192

issn

1096-7206

pii

S1096-7192(08)00253-9

journal_volume

96

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

  • A Delphi-based consensus clinical practice protocol for the diagnosis and management of 3-methylcrotonyl CoA carboxylase deficiency.

    abstract：:3-MCC deficiency is among the most common inborn errors of metabolism identified on expanded newborn screening (1:36,000 births). However, evidence-based guidelines for diagnosis and management of this disorder are lacking. Using the traditional Delphi method, a panel of 15 experts in inborn errors of metabolism was c...

    journal_title：Molecular genetics and metabolism

    pub_type： 共识发展会议,杂志文章,实务指引

    doi：10.1016/j.ymgme.2007.11.002

    authors： Arnold GL,Koeberl DD,Matern D,Barshop B,Braverman N,Burton B,Cederbaum S,Fiegenbaum A,Garganta C,Gibson J,Goodman SI,Harding C,Kahler S,Kronn D,Longo N

    更新日期：2008-04-01 00:00:00

  • The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

    abstract：:Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-a...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2013.06.014

    authors： Lee YM,Pan CJ,Koeberl DD,Mansfield BC,Chou JY

    更新日期：2013-11-01 00:00:00

  • ELMO1 variants and susceptibility to diabetic nephropathy in American Indians.

    abstract：:Variants in the engulfment and cell motility 1 gene, ELMO1, have previously been associated with kidney disease attributed to type 2 diabetes. The Pima Indians of Arizona have high rates of diabetic nephropathy, which is strongly dependent on genetic determinants; thus, we sought to investigate the role of ELMO1 polym...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2010.08.014

    authors： Hanson RL,Millis MP,Young NJ,Kobes S,Nelson RG,Knowler WC,DiStefano JK

    更新日期：2010-12-01 00:00:00

  • Maternal medium-chain acyl-CoA dehydrogenase deficiency identified by newborn screening.

    abstract：:Prior to the advent of expanded newborn screening, sudden and unexplained death was often the first and only symptom of medium-chain acyl-CoA dehydrogenase deficiency (MCADD). With the use of tandem mass spectrometry, infants can now be identified and treated before a life threatening metabolic decompensation occurs. ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2011.01.011

    authors： Leydiker KB,Neidich JA,Lorey F,Barr EM,Puckett RL,Lobo RM,Abdenur JE

    更新日期：2011-05-01 00:00:00

  • Polygenic association with total homocysteine in the post-folic acid fortification era: the CARDIA study.

    abstract：:Elevated plasma concentration of total homocysteine (tHcy) has been linked with many diseases. tHcy is associated with a variety of factors, including polymorphisms in genes involved in homocysteine metabolism. It is not clear whether US-mandated fortification of grain products with folic acid has affected the associa...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2009.05.012

    authors： Tsai MY,Loria CM,Cao J,Kim Y,Siscovick DS,Schreiner PJ,Hanson NQ

    更新日期：2009-09-01 00:00:00

  • Prevalence and predictors of liver fibrosis evaluated by vibration controlled transient elastography in type 1 Gaucher disease.

    abstract：BACKGROUND & AIMS:Long-term liver-related complications of Gaucher disease (GD) include cirrhosis, portal hypertension and hepatocellular carcinoma. Although liver fibrosis is the main determinant of adverse liver-related clinical outcomes, it has rarely been evaluated in previously published cohorts of GD patients. We...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2018.08.004

    authors： Nascimbeni F,Cassinerio E,Dalla Salda A,Motta I,Bursi S,Donatiello S,Spina V,Cappellini MD,Carubbi F

    更新日期：2018-09-01 00:00:00

  • Analysis of FOXO1A as a candidate gene for type 2 diabetes.

    abstract：:The human forkhead box O1A (FOXO1A) gene on chromosome 13q14.1 is a key transcription factor in insulin signaling in liver and adipose tissue and plays a central role in the regulation of key pancreatic beta-cell genes including IPF1. We hypothesized that sequence variants of FOXO1A contribute to the observed defects ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2006.01.003

    authors： Karim MA,Craig RL,Wang X,Hale TC,Elbein SC

    更新日期：2006-06-01 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

  • Mutation in a putative glycosylation site (N489T) of biotinidase in the only known Japanese child with biotinidase deficiency.

    abstract：:The only known Japanese child with biotinidase deficiency was identified by newborn screening in Japan. He has 10.8% of mean normal serum biotinyl-hydrolase activity and trace biotinyl-transferase activity. The mutation results in 16% of normal cross-reacting material in serum with antibody to purified normal biotinid...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.1998.2706

    authors： Pomponio RJ,Yamaguchi A,Arashima S,Hymes J,Wolf B

    更新日期：1998-06-01 00:00:00

  • Investigation of folate pathway gene polymorphisms and the incidence of neural tube defects in a Texas hispanic population.

    abstract：:Neural tube defects (NTDs) are multifactorial in their etiology, having both genetic and environmental factors contributing to their development. Recent evidence demonstrates that periconceptional supplementation of the maternal diet with a multivitamin containing folic acid significantly reduces the occurrence and re...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2000.2991

    authors： Barber R,Shalat S,Hendricks K,Joggerst B,Larsen R,Suarez L,Finnell R

    更新日期：2000-05-01 00:00:00

  • Psychosine, a marker of Krabbe phenotype and treatment effect.

    abstract：:Newborn screening (NBS) for Krabbe disease, a rare neurodegenerative disorder caused by deficient galactocerebrosidase (GALC) enzyme activity, has recently been implemented in a number of US states. However, the spectrum of phenotypic manifestations associated with deficient GALC activity complicates the management of...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2017.05.015

    authors： Escolar ML,Kiely BT,Shawgo E,Hong X,Gelb MH,Orsini JJ,Matern D,Poe MD

    更新日期：2017-07-01 00:00:00

  • A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4.

    abstract：:Congenital generalized lipodystrophy (CGL), characterized by generalized absence of adipose tissue, has heterogeneous causes. Recently, a novel type of CGL complicated by muscular dystrophy was categorized as CGL4 caused by PTRF-CAVIN deficiency. However, it is unknown whether CGL4 exhibits clinical abnormalities duri...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2010.06.016

    authors： Dwianingsih EK,Takeshima Y,Itoh K,Yamauchi Y,Awano H,Malueka RG,Nishida A,Ota M,Yagi M,Matsuo M

    更新日期：2010-10-01 00:00:00

  • Application of oligonucleotide array CGH to the simultaneous detection of a deletion in the nuclear TK2 gene and mtDNA depletion.

    abstract：:Thymidine kinase 2 (TK2), encoded by the TK2 gene on chromosome 16q22, is one of the deoxyribonucleoside kinases responsible for the maintenance of mitochondrial deoxyribonucleotide pools. Defects in TK2 mainly cause a myopathic form of the mitochondrial DNA depletion syndrome (MDDS). Currently, only point mutations a...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2009.09.003

    authors： Zhang S,Li FY,Bass HN,Pursley A,Schmitt ES,Brown BL,Brundage EK,Mardach R,Wong LJ

    更新日期：2010-01-01 00:00:00

  • Glycan-based biomarkers for mucopolysaccharidoses.

    abstract：:The mucopolysaccharidoses (MPS) result from attenuation or loss of enzyme activities required for lysosomal degradation of the glycosaminoglycans, hyaluronan, heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate. This review provides a summary of glycan biomarkers that have been used to characterize anim...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1016/j.ymgme.2013.07.016

    authors： Lawrence R,Brown JR,Lorey F,Dickson PI,Crawford BE,Esko JD

    更新日期：2014-02-01 00:00:00

  • Genetic variation of the ATP-binding cassette transporter A1 and susceptibility to coronary heart disease.

    abstract：:ATP-binding cassette transporter A1 (ABCA1) is a member of a superfamily of membrane proteins that has attracted considerable attention as a candidate gene for coronary heart disease (CHD) based on its enzyme function as a key factor in regulating plasma HDL-C and apo A-I metabolism. It has been suggested that polymor...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,meta分析

    doi：10.1016/j.ymgme.2011.01.005

    authors： Jiang Z,Zhou R,Xu C,Feng G,Zhou Y

    更新日期：2011-05-01 00:00:00

  • Elevated plasma dihydroorotate in Miller syndrome: Biochemical, diagnostic and clinical implications, and treatment with uridine.

    abstract：BACKGROUND:Miller syndrome (post-axial acrofacial dysostosis) arises from gene mutations for the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). Nonetheless, despite demonstrated loss of enzyme activity dihydroorotate (DHO) has not been shown to accumulate, but paradoxically urine orotate has been reported t...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2016.06.008

    authors： Duley JA,Henman MG,Carpenter KH,Bamshad MJ,Marshall GA,Ooi CY,Wilcken B,Pinner JR

    更新日期：2016-09-01 00:00:00

  • Tetrahydrobiopterin responsiveness in phenylketonuria differs between patients with the same genotype.

    abstract：:Recently, BH(4)-responsive phenylalanine hydroxylase (PAH) deficiency was reported in patients with specific mutations in the PAH gene, and it was suggested that BH(4) responsiveness may be determined by the respective genotypes. We now report on three patients with PAH deficiency and the same genotype but different r...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2001.3168

    authors： Lindner M,Haas D,Mayatepek E,Zschocke J,Burgard P

    更新日期：2001-05-01 00:00:00

  • Characterization of urinary sulfatides in metachromatic leukodystrophy using electrospray ionization-tandem mass spectrometry.

    abstract：:Metachromatic leukodystrophy is an inherited disorder characterized by a deficiency of the lysosomal enzyme arylsulfatase A and the subsequent accumulation of sulfatide in neural and visceral tissues. Clinical diagnosis is usually confirmed by in vitro analysis of arylsulfatase A activity, but may be complicated in ca...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1006/mgme.2001.3165

    authors： Whitfield PD,Sharp PC,Johnson DW,Nelson P,Meikle PJ

    更新日期：2001-05-01 00:00:00

  • Identification of a novel TPM1 mutation in a family with left ventricular noncompaction and sudden death.

    abstract：:Left ventricular noncompaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses communicating with the left ventricular cavity. The purpose of this study was to investigate patients with LVNC for possible disease caus...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2010.09.009

    authors： Chang B,Nishizawa T,Furutani M,Fujiki A,Tani M,Kawaguchi M,Ibuki K,Hirono K,Taneichi H,Uese K,Onuma Y,Bowles NE,Ichida F,Inoue H,Matsuoka R,Miyawaki T,Noncompaction study collaborators.

    更新日期：2011-02-01 00:00:00

  • Sensitive quantification of mosaicism using high density SNP arrays and the cumulative distribution function.

    abstract：:Medicine is rapidly applying exome and genome sequencing to the diagnosis and management of human disease. Somatic mosaicism, however, is not readily detectable by these means, and yet it accounts for a significant portion of undiagnosed disease. We present a rapid and sensitive method, the Continuous Distribution Fun...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2011.12.015

    authors： Markello TC,Carlson-Donohoe H,Sincan M,Adams D,Bodine DM,Farrar JE,Vlachos A,Lipton JM,Auerbach AD,Ostrander EA,Chandrasekharappa SC,Boerkoel CF,Gahl WA

    更新日期：2012-04-01 00:00:00

  • Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh gene.

    abstract：:We report here the case of a young male who started to show verbal fluency disturbance, clumsiness and gait anomalies at the age of 3.5years and presented bilateral striatal necrosis. Clinically, the diagnosis was compatible with Leigh syndrome but the underlying molecular defect remained elusive even after exome anal...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2016.09.001

    authors： Bianciardi L,Imperatore V,Fernandez-Vizarra E,Lopomo A,Falabella M,Furini S,Galluzzi P,Grosso S,Zeviani M,Renieri A,Mari F,Frullanti E

    更新日期：2016-11-01 00:00:00

  • Correlating liver stiffness with disease severity scoring system (DS3) values in Gaucher disease type 1 (GD1) patients.

    abstract：:Gaucher disease (GD) is an autosomal-recessive lysosomal storage disease caused by a deficiency of the enzyme, glucocerebrocidase, resulting in accumulation of lipid-laden storage cells in multiple organs such as bone marrow, liver, spleen, and lungs. Type 1 Gaucher disease is the most common form of this condition in...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2017.10.013

    authors： Serai SD,Naidu AP,Andrew Burrow T,Prada CE,Xanthakos S,Towbin AJ

    更新日期：2018-03-01 00:00:00

  • 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25-dihydroxy vitamin D3: production and biological activity studies in pulmonary alveolar type II cells.

    abstract：:Pulmonary alveolar type II cells have been shown to be a possible target for the secosteroid hormone, 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3], during perinatal transition. At present, there is great interest to isolate and identify the metabolites of 1alpha,25(OH)2D3 produced in its target tissues and to dete...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/s1096-7192(02)00022-7

    authors： Rehan VK,Torday JS,Peleg S,Gennaro L,Vouros P,Padbury J,Rao DS,Reddy GS

    更新日期：2002-05-01 00:00:00

  • Characterization of two deletions of the CTRC locus.

    abstract：:Novel variants associated with chronic pancreatitis are being increasingly reported. However, most studies have so far only analyzed point mutations and small insertions or deletions. Here we report the characterization of two distinct deletions of the CTRC locus. Variants in four chronic pancreatitis genes, PRSS1, SP...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2013.04.022

    authors： Masson E,Hammel P,Garceau C,Bénech C,Quéméner-Redon S,Chen JM,Férec C

    更新日期：2013-07-01 00:00:00

  • Plasma total homocysteine concentrations in adults with growth hormone (GH) deficiency: effects of GH replacement.

    abstract：:Growth hormone (GH) deficiency is associated with increased cardiovascular morbidity and mortality. GH treatment improves the profile of many cardiovascular risk markers in individuals with GH deficiency (GHD). The aim of the present was to assess whether GH replacement may decrease plasma total homocysteine, an indep...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2003.08.020

    authors： Lewandowski KC,Murray RD,Drzewoski J,O'Callaghan CJ,Czupryniak L,Hillhouse EW,Shalet SM,Randeva HS

    更新日期：2003-11-01 00:00:00

  • Characterization of phytanic acid omega-hydroxylation in human liver microsomes.

    abstract：:Phytanic acid is a 3-methyl branched-chain fatty acid which originates from dietary sources. Since the 3-methyl group blocks regular beta-oxidation, it is broken down by peroxisomal alpha-oxidation. Adult Refsum disease patients accumulate phytanic acid as a result of an impairment in peroxisomal alpha-oxidation, caus...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章

    doi：10.1016/j.ymgme.2005.02.005

    authors： Komen JC,Duran M,Wanders RJ

    更新日期：2005-07-01 00:00:00

  • Nonexpressing homozygotes for C282Y hemochromatosis: minority or majority of cases?

    abstract：:Genetic testing for the C282Y mutation of the HFE gene has been a major advance in the diagnosis of hereditary hemochromatosis. In most studies, more than 90% of typical hemochromatosis patients are homozygous for the C282Y mutation. Large-scale population screening studies in predominantly Caucasian populations have ...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,评审

    doi：10.1006/mgme.2000.3037

    authors： Adams PC

    更新日期：2000-09-01 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

  • Improved muscle function in a phase I/II clinical trial of albuterol in Pompe disease.

    abstract：:This 24-week, Phase I/II, double-blind, randomized, placebo-controlled study investigated the safety and efficacy of extended-release albuterol in late-onset Pompe disease stably treated with enzyme replacement therapy at the standard dose for 4.9 (1.0-9.4) years and with no contraindications to intake of albuterol. T...

    journal_title：Molecular genetics and metabolism

    pub_type： 杂志文章,随机对照试验

    doi：10.1016/j.ymgme.2019.12.008

    authors： Koeberl DD,Case LE,Desai A,Smith EC,Walters C,Han SO,Thurberg BL,Young SP,Bali D,Kishnani PS

    更新日期：2020-02-01 00:00:00