Abstract：
:DAX1 encoded by NR0B1, when mutated, is responsible for X-linked adrenal hypoplasia congenita (AHC). AHC is due to failure of the adrenal cortex to develop normally and is fatal if untreated. When duplicated, this gene is associated with an XY sex-reversed phenotype. DAX1 expression is present during development of the steroidogenic hypothalamic-pituitary-adrenal-gonadal (HPAG) axis and persists into adult life. Despite recognition of the crucial role for DAX1, its function remains largely undefined. The phenotypes of patients and animal models are complex and not always in agreement. Investigations using cell lines have proved difficult to interpret, possibly reflecting cell line choices and their limited characterization. We will review the efforts of our group and others to identify appropriate cell lines for optimizing ex vivo analysis of NR0B1 function throughout development. We will examine the role of DAX1 and its network partners in development of the hypothalamic-pituitary-adrenal/gonadal axis (HPAG) using a variety of different types of investigations, including those in model organisms. This network analysis will help us to understand normal and abnormal development of the HPAG. In addition, these studies permit identification of candidate genes for human inborn errors of HPAG development.
journal_name
Mol Genet Metabjournal_title
Molecular genetics and metabolismauthors
Clipsham R,McCabe ERdoi
10.1016/j.ymgme.2003.08.023subject
Has Abstractpub_date
2003-09-01 00:00:00pages
81-120issue
1-2eissn
1096-7192issn
1096-7206pii
S1096719203001793journal_volume
80pub_type
杂志文章,评审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：: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：:Quantitative fluorescent multiplex PCR (QFM-PCR) was established in order to make possible the rapid and efficient mutational analysis of the pancreatic secretory trypsin inhibitor (SPINK1) gene. Using QFM-PCR, a novel heterozygous deletion encompassing the entire SPINK1 gene was identified in one of nine newly recrui...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2007.06.006
更新日期：2007-09-01 00:00:00
abstract：UNLABELLED:The phenotype of attenuated mucopolysaccharidosis type II (MPS II), also called Hunter syndrome, has not been previously studied in systematic manner. In contrast to the "severe" phenotype, the "attenuated" phenotype does not present with behavioral or cognitive impairment; however, the presence of mild beha...
journal_title：Molecular genetics and metabolism
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1016/j.ymgme.2014.12.299
更新日期：2015-02-01 00:00:00
abstract：:Accumulations of glycosaminoglycans (GAGs) that result from deficiencies in lysosomal hydrolases are characteristic of mucopolysaccharidoses (MPS). Enzyme replacement therapies (ERTs) are now available for several MPS diseases (MPS I, MPS II, MPS IVA, MPS VI, and MPS VII), but assessment of the efficacy of treatment c...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.ymgme.2020.02.006
更新日期：2020-05-01 00:00:00
abstract：:Lung dysfunction is an important part of the pathology of the neurodegenerative disorder, Niemann-Pick C1 (NPC1). We have studied the pulmonary disease in the Npc1(NIH/NIH) mouse model. On histology, we find large numbers of alveolar foamy macrophages but no alveolar proteinosis. Lung weight as percent of body weight ...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2011.03.001
更新日期：2011-06-01 00:00:00
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
更新日期：2010-06-01 00:00:00
abstract：:Suppression therapy utilizes compounds that suppress translation termination at in-frame premature termination codons (PTCs) to restore full-length, functional protein. This approach may provide a treatment for diseases caused by nonsense mutations such as mucopolysaccharidosis type I-Hurler (MPS I-H). MPS I-H is a ly...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2011.10.005
更新日期：2012-01-01 00:00:00
abstract：:Oxidative stress plays an important role in the pathophysiology of neurodegenerative diseases, including X-linked adrenoleukodystrophy (X-ALD). In the present work, we evaluated lipid (malondialdehyde [MDA] content) and protein (sulfhydryl and carbonyl contents) oxidative damage parameters in plasma from X-ALD patient...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2012.03.019
更新日期：2012-06-01 00:00:00
abstract：:Mitochondrial diseases are a clinically and genetically heterogeneous group of disorders that result from dysfunction of the mitochondrial oxidative phosphorylation due to molecular defects in genes encoding mitochondrial proteins. Despite the advances in molecular and biochemical methodologies leading to better under...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.ymgme.2017.09.009
更新日期：2017-11-01 00:00:00
abstract：:Inborn defects of cholesterol biosynthesis are metabolic disorders presenting with multi-organ and tissue anomalies. An autosomal recessive defect involving the demethylating enzyme C4-methyl sterol (SC4MOL) has been reported in only 4 patients so far. In infancy, all patients were affected by microcephaly, bilateral ...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2017.06.013
更新日期：2017-08-01 00:00:00
abstract：:The disorder trimethylaminuria (TMAu) often manifests itself in a body odor for individuals affected. TMAu is due to decreased metabolism of dietary-derived trimethylamine (TMA). In a healthy individual, 95% or more of TMA is converted by the flavin-containing monooxygenase 3 (FMO3, EC 1.14.13.8) to non-odorous trimet...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2009.02.006
更新日期：2009-06-01 00:00:00
abstract：:Pompe disease is caused by the deficiency of lysosomal acid α-glucosidase (GAA) leading to progressive myopathy. Enzyme replacement therapy (ERT) with recombinant human (rh) GAA has limitations, including inefficient uptake of rhGAA in skeletal muscle linked to low cation-independent mannose-6-phosphate receptor (CI-M...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2019.10.005
更新日期：2020-02-01 00:00:00
abstract：:To elucidate the basis of mucopolysaccharidosis type VI (MPS VI) from the point of view of enzyme structure, we built structural models of mutant N-acetylgalactosamine-4-sulfatase (4S) resulting from 34 missense mutations (17 severe and 17 attenuated), and analyzed the influence of each amino acid replacement on the s...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2007.11.017
更新日期：2008-04-01 00:00:00
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
更新日期：2002-05-01 00:00:00
abstract：:Hypotonia-cystinuria syndrome (HCS) is an autosomal recessive disorder caused by combined deletions of SLC3A1 and PREPL. Clinical features include cystinuria, neonatal hypotonia with spontaneous improvement, poor feeding in neonates, hyperphagia in childhood, growth hormone deficiency, and variable cognitive problems....
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2012.06.011
更新日期：2012-11-01 00:00:00
abstract：:Acute intermittent porphyria (AIP) is an autosomal dominant disorder of heme biosynthesis caused by molecular defects in the hydroxymethylbilane synthase (HMBS) gene. In this study, we report two novel missense sequence variations in the HMBS gene, T59I (C176T) and V215M (G643A), in two patients with clinical symptoms...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2008.03.001
更新日期：2008-07-01 00:00:00
abstract：:Cystic Fibrosis (CF) is an autosomal recessive disorder affecting 1/2000-4000 newborns in Caucasian populations. This lethal disease mainly affects respiratory and digestive organs as well as fertility in man. So far, the CF prevalence and mutational spectrum have showed specificity among populations and regions, maki...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2005.12.001
更新日期：2006-04-01 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：: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
更新日期：2012-04-01 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：:1,2,3-Benzenetricarboxylate (BTA) and n-butylmalonate (BM), specific inhibitors of the mitochondrial tricarboxylate and dicarboxylate carrier, respectively, have been used to study the contribution of citrate export from mitochondria to the accumulation of fat in 3T3-L1 cells. Continuous treatment of the cells with BT...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2005.01.006
更新日期：2005-05-01 00:00:00
abstract：:Screening for Smith-Lemli-Opitz Syndrome (SLOS) using elevated 7-dehydrocholesterol (7DHC) as a marker is sensitive, but not always specific. Elevations of 7DHC can be seen in patients who do not have a defect in 7-dehydrocholesterol reductase. These results have often been attributed to medication artifacts, but spec...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2013.04.004
更新日期：2013-09-01 00:00:00
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
更新日期：2001-05-01 00:00:00
abstract：:Saposin A is a post-translation product of the prosaposin (PSAP) gene that serves as an activator protein of the galactocerebrosidase (GALC) enzyme, and is necessary for the degradation of certain glycosphingolipids. Deficiency of saposin A leads to a clinical picture identical to that of early-infantile Krabbe diseas...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2019.08.001
更新日期：2020-02-01 00:00:00
abstract：:A six-day-old girl was referred for severe hepatic failure, dehydratation, axial hypotonia, and both lactic acidosis and ketoacidosis. Biotin-unresponsive pyruvate carboxylase deficiency type B was diagnosed. Triheptanoin, an odd-carbon triglyceride, was administrated as a source for acetyl-CoA and anaplerotic propion...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1016/j.ymgme.2004.09.007
更新日期：2005-04-01 00:00:00
abstract：:Ornithine transcarbamylase deficiency is a very heterogeneous urea cycle disorder resulting in hyperammonemia with various presentations from the neonatal period through adulthood. We performed a retrospective study in nine patients (four male/five female, age at diagnosis ranging from 6 days to 14 years) to evaluate ...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章
doi：10.1006/mgme.2001.3156
更新日期：2001-04-01 00:00:00
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
更新日期：2016-09-01 00:00:00
abstract：:Dyggve-Melchior-Clausen (DMC) is a rare autosomal-recessive disorder characterized by the association of a progressive spondylo-epi-metaphyseal dysplasia and mental retardation ranging from mild to severe. Electron microscopy studies of both DMC chondrocytes and fibroblasts reveal an enlarged endoplasmic reticulum net...
journal_title：Molecular genetics and metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.ymgme.2004.08.012
更新日期：2004-09-01 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
