Abstract:
:For a population-based newborn screening program, challenges exist in using technological advances to improve the quality and efficiency of the existing screening program and to develop new diagnostic capabilities. A newly developed genotyping method for screening of common mutations within the beta-globin gene is described here. This genotyping system consists of three major components: an automation system for high throughput DNA extraction and PCR setup, a conventional thermal cycler, and a LightTyper instrument for post-PCR melting temperature analysis. Briefly, genomic DNA is extracted from dried blood on a filter paper using methanol and Tris buffer. Genetic fragments of interest are amplified by asymmetric PCR. Fluorescent labeled probes are added during PCR setup, which eliminates the need for any post-PCR sample handling process. Melting temperature analysis is achieved through fluorescent resonance energy transfer (FRET) reaction using the LightTyper instrument. The assay is designed to simultaneously detect three common beta-globin mutations, S(A173T), C(G172A), and E(G232A), and can identify any of the eight possible genotypes in a single reaction: AA, AE, EE, AS, SC, SS, AC, and CC (A represents wild type allele). The method was validated with a large number of samples in both a retrospective and parallel study. Results were compared to those obtained by isoelectric focusing electrophoresis. The accuracy of this genotyping method is greater than 99%.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Lin Z,Suzow JG,Fontaine JM,Naylor EWdoi
10.1016/j.ymgme.2003.12.007subject
Has Abstractpub_date
2004-03-01 00:00:00pages
237-43issue
3eissn
1096-7192issn
1096-7206pii
S1096719203002865journal_volume
81pub_type
杂志文章abstract::Fabry disease is a lysosomal storage disease caused by deficient activity of the α-Galactosidase A (α-Gal A) enzyme, which leads to abnormal accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), in the lysosome. Glycosphingolipids are known to be invariant Natural Killer T (iNKT) cell antigens. Sever...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.02.014
更新日期:2012-05-01 00:00:00
abstract::Neutral lipid storage disease with myopathy (NLSD-M) is a rare autosomal recessive disorder characterised by an abnormal accumulation of triacylglycerol into cytoplasmic lipid droplets (LDs). NLSD-M patients are mainly affected by progressive myopathy, cardiomyopathy and hepatomegaly. Mutations in the PNPLA2 gene caus...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.05.001
更新日期:2015-06-01 00:00:00
abstract::Infantile hepatopathies are life-threatening liver disorders that manifest in the first few months of life. We report on a consanguineous Irish Traveller family that includes six individuals presenting with acute liver failure in the first few months of life. Additional symptoms include anaemia, renal tubulopathy, dev...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2012.04.017
更新日期:2012-07-01 00:00:00
abstract::3-Hydroxy-3-methylglutaryl-CoA lyase (HL) deficiency is a rare autosomal recessive genetic disorder that affects ketogenesis and l-leucine catabolism, which generally appears during the first year of life. Patients with HL deficiency have a reduced capacity to synthesize ketone bodies. The disease is caused by lethal ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2007.06.020
更新日期:2007-11-01 00:00:00
abstract::A stop codon defect in methylmalonyl-CoA mutase (resulting in a truncated unstable protein) accounts for up to 14% of mutations identified as causes of Methylmalonic aciduria. There are currently limited treatment regimes for patients with this inherited condition. We aimed to investigate the use of stop codon read-th...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2009.04.004
更新日期:2009-08-01 00:00:00
abstract::Solubilized A1 adenosine receptor (A1AR) was used to investigate the effect of several cations on agonist-binding characteristics and GTP hydrolysis. It was shown by Western blot with G beta-M14 that this preparation contains both G proteins and receptor. The role of the receptor molecule is to facilitate the activati...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.1997.2674
更新日期:1998-03-01 00:00:00
abstract::N-acetylglutamate (NAG) is a unique enzyme cofactor, essential for liver ureagenesis in mammals while it is the first committed substrate for de novo arginine biosynthesis in microorganisms and plants. The enzyme that produces NAG from glutamate and CoA, NAG synthase (NAGS), is allosterically inhibited by arginine in ...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2010.02.018
更新日期:2010-01-01 00:00:00
abstract::Tetrahydrobiopterin (BH(4)) is widely used as a therapeutic agent in patients with BH(4) deficiencies and mild forms of phenylketonuria (PKU) and there is an increasing need for the measurement of its plasma concentrations in patients with cardiovascular disorders. We measured BH(4) and total biopterin in dithioerythr...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2003.09.014
更新日期:2004-01-01 00:00:00
abstract::The enzymatic defect in Pompe disease is insufficient lysosomal acid alpha-glucosidase (GAA) activity which leads to lysosomal glycogen accumulation. We recently introduced a simple and reliable method to measure GAA activity in dried blood spots using Acarbose, a highly selective alpha-glucosidase inhibitor, to elimi...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2006.12.006
更新日期:2007-04-01 00:00:00
abstract:BACKGROUND:There appears little consensus concerning protein requirements in phenylketonuria (PKU). METHODS:A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.03.006
更新日期:2015-05-01 00:00:00
abstract::The Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by ponto-bulbar palsy, bilateral sensorineural deafness, and respiratory insufficiency. Recent genetic studies have identified mutations in the C20orf54 gene, which encodes the human riboflavin (RF) transporter -2 (hRFT-2) and s...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2011.12.021
更新日期:2012-04-01 00:00:00
abstract::The disorders of purine and pyrimidine metabolism are unusual in their variety of clinical presentations and in the mechanisms by which these presentations result from the fundamental mutations. In the most common of the hyperuricemic metabolic disorders, deficiency of hypoxanthine phosphoribosyl transferase, the fund...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.ymgme.2005.07.027
更新日期:2005-09-01 00:00:00
abstract::Phenylalanine hydroxylase (PAH) deficiency, colloquially known as phenylketonuria (PKU), is among the most common inborn errors of metabolism and in the past decade has become a target for the development of novel therapeutics such as gene therapy. PAH deficient mouse models have been key to new treatment development,...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2020.09.005
更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Obstructive sleep apnea syndrome (OSAS) is very common in mucopolysaccharidosis I (MPS I). Hematopoietic stem cell transplantation (HSCT) is the preferred treatment for patients with severe MPS I diagnosed early in life. The protective effect of HSCT on the development of long term OSAS is not known. METHOD...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2015.10.004
更新日期:2015-12-01 00:00:00
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
更新日期:2001-05-01 00:00:00
abstract::Recent studies indicate altered cholesterol homeostasis in Huntington's disease (HD) after it was found that cultured human and mice cells expressing mutant huntingtin show reduced mRNA of cholesterol biosynthetic enzymes. Plasma total cholesterol (TC) levels have been connected to degenerative disorders, but data for...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2007.10.002
更新日期:2008-03-01 00:00:00
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
更新日期:2006-06-01 00:00:00
abstract::Previous studies from this laboratory have shown that maternal-derived cholesterol can be effluxed from trophoblasts to fetal HDL and plasma. We had the opportunity to study for the first time the ability of HDL and plasma from a fetus with the Smith-Lemli-Opitz syndrome (SLOS) to efflux cholesterol from trophoblasts....
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2008.01.015
更新日期:2008-06-01 00:00:00
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
更新日期:1998-10-01 00:00:00
abstract::Glycogen storage disease type I (GSD I) is caused by inherited defects of the glucose 6-phosphatase complex, resulting in fasting hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia. Sixteen out of 26 (61.5%) GSD I patients in our study had suboptimal levels (<30 ng/ml) of 25-hydroxyvitamin-D (25(OH)D) des...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2009.12.012
更新日期:2010-04-01 00:00:00
abstract::Isovaleric acidemia (IVA), a rare recessive autosomal disorder, is caused by isovaleryl-CoA dehydrogenase (IVD) deficiency. IVA may present with symptoms during the acute stage of severe metabolic acidosis, ketosis, vomiting, and altered mental status. With the help of newborn screening (NBS) by tandem mass spectromet...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2006.08.011
更新日期:2007-02-01 00:00:00
abstract::We recently reported that PAF acetylhydrolase (PAF-Ah) mRNA level and PAF-Ah activity in lamb lungs are up-regulated in the immediate newborn period, thereby facilitating the fall in postnatal PAF levels as well as a fall in pulmonary vascular resistance (B. O. Ibe, F. C. Sardar, and J. U. Raj, Mol Genet Metab 69:46-5...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1006/mgme.2001.3253
更新日期:2001-11-01 00:00:00
abstract::Abnormal neurodevelopment has been widely reported in combined methylmalonic aciduria (MMA) and homocystinuria, cblC type (cblC disease), but neurodevelopmental phenotypes in cblC have not previously been systematically studied. We sought to further characterize developmental neurology in children with molecularly-con...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2013.07.018
更新日期:2013-11-01 00:00:00
abstract:INTRODUCTION:Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is me...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2019.01.011
更新日期:2019-04-01 00:00:00
abstract::Leigh syndrome is a progressive neurodegenerative disorder occurring in infancy and childhood characterized in most cases by a psychomotor retardation, optic atrophy, ataxia, dystonia, failure to thrive, seizures and respiratory failure. In this study, we performed a systematic sequence analysis of mitochondrial genes...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2009.03.003
更新日期:2009-07-01 00:00:00
abstract::Mucopolysaccharidosis type II (MPS II: also called as Hunter syndrome) is an X-linked recessive lysosomal storage disorder characterized by the accumulation of extracellular glycosaminoglycans due to the deficiency of the enzyme iduronate-2-sulfatase (IDS). Previous observations suggested that MPS II can be classified...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2016.05.003
更新日期:2016-07-01 00:00:00
abstract::The association of fetal hydrops with Congenital Disorders of Glycosylation (CDG) has been reported previously. Pericardial fluid accumulation and ascites were also observed in a few young patients with CDG type Ia. Here we describe the clinical and biochemical features in three children developing life-threatening ex...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2008.05.005
更新日期:2008-08-01 00:00:00
abstract::Pyruvate dehydrogenase complex (PDC) deficiency is one of the major recognized causes of congenital lactic acidosis. The most common form is due to PDHA 1 gene (Xp22.12) defects. Here, we report the case of a Polynesian girl presenting with delayed neurological development, cortical atrophy, and posterior corpus callo...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2005.08.009
更新日期:2005-12-01 00:00:00
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
更新日期:2003-11-01 00:00:00
abstract::Patients with neonatal urea cycle defects (UCDs) typically have high mortality and poor neurological outcome unless they receive liver transplantation. Neurologic outcome may be better with liver transplantation before age one year. We report on a follow up on an initial prospective study performed to assess developme...
journal_title:Molecular genetics and metabolism
pub_type: 杂志文章
doi:10.1016/j.ymgme.2010.02.012
更新日期:2010-01-01 00:00:00