Read by QxMD icon Read

Molecular Genetics and Metabolism

Nayiri Kaissarian, Justin Kang, Liming Shu, Maria J Ferraz, Johannes M Aerts, James A Shayman
Fabry disease, a rare, X-linked lysosomal storage disease, arises from deficiency of the lysosomal hydrolase, α-galactosidase A (GLA) which disrupts the catabolism of globo- series glycosphingolipids (GSLs). One potential link between GLA deficiency and vascular dysfunction may be changes in endothelial nitric oxide synthase (eNOS) function. GLA-deficient EA.hy926 cells were obtained by siRNA knockdown of GLA expression and by mutation of GLA with CRISPR/Cas9 gene editing to investigate the effects of GLA deficiency on eNOS...
November 2, 2018: Molecular Genetics and Metabolism
A Cougnoux, S Clifford, A Salman, S-L Ng, J Bertin, F D Porter
Niemann-Pick disease, type C1 (NPC1) is an inborn error of metabolism that results in endolysosomal accumulation of unesterified cholesterol. Clinically, NPC1 manifests as cholestatic liver disease in the newborn or as a progressive neurogenerative condition characterized by cerebellar ataxia and cognitive decline. Currently there are no FDA approved therapies for NPC1. Thus, understanding the pathological processes that contribute to neurodegeneration will be important in both developing and testing potential therapeutic interventions...
October 30, 2018: Molecular Genetics and Metabolism
Yonina Loskove, Makiko Yasuda, Brenden Chen, Irina Nazarenko, Neal Cody, Robert J Desnick
The acute hepatic porphyrias (AHPs) are inborn errors of heme biosynthesis, which include three autosomal dominant porphyrias, Acute Intermittent Porphyria (AIP), Hereditary Coproporphyria (HCP), and Variegate Porphyria (VP), and the ultra-rare autosomal recessive porphyria, δ-Aminolevulinic Acid Dehydratase Deficiency Porphyria (ADP). AIP, HCP, VP, and ADP each results from loss-of-function (LOF) mutations in their disease-causing genes: hydroxymethylbilane synthase (HMBS); coproporphyrinogen oxidase (CPOX); protoporphyrinogen oxidase (PPOX), and δ-aminolevulinic acid dehydratase (ALAD), respectively...
October 26, 2018: Molecular Genetics and Metabolism
John Phillips, Collin Farrell, Yongming Wang, Ashwani K Singal, Karl Anderson, Manisha Balwani, Montgomery Bissell, Herbert Bonkovsky, Toni Seay, Barry Paw, Robert Desnick, Joseph Bloomer
Accumulation of protoporphyrin IX (PPIX) and Zn-PPIX, are the clinical hallmarks of protoporphyria. Phenotypic expression of protoporphyria is due to decreased activity of ferrochelatase (FECH) or to increased activity of aminolevulinic acid synthase (ALAS) in red blood cells. Other genetic defects have been shown to contribute to disease severity including loss of function mutations in the mitochondrial AAA-ATPase, CLPX and mutations in the Iron-responsive element binding protein 2 (IRP2), in mice. It is clear that multiple paths lead to a common phenotype of excess plasma PPIX that causes a phototoxic reaction on sun exposed areas...
October 22, 2018: Molecular Genetics and Metabolism
Christopher Newell, Stacey Hume, Steven C Greenway, Lynn Podemski, Jane Shearer, Aneal Khan
BACKGROUND: Mitochondrial diseases are a clinically heterogeneous group of diseases caused by mutations in either nuclear or mitochondrial DNA (mtDNA). The diagnosis is challenging and has frequently required a tissue biopsy to obtain a sufficient quantity of mtDNA. Less-invasive sources mtDNA, such as peripheral blood leukocytes, urine sediment, or buccal swab, contain a lower quantity of mtDNA compared to tissue sources which may reduce sensitivity. Cellular apoptosis of tissues and hematopoetic cells releases fragments of DNA and mtDNA into the circulation and these molecules can be extracted from plasma as cell-free DNA (cfDNA)...
October 16, 2018: Molecular Genetics and Metabolism
Ayman W El-Hattab, Jehan Suleiman, Mohammed Almannai, Fernando Scaglia
Mitochondria are dynamic organelles that undergo fusion, fission, movement, and mitophagy. These processes are essential to maintain the normal mitochondrial morphology, distribution, and function. Mitochondrial fusion allows the exchange of intramitochondrial material, whereas the fission process is required to replicate the mitochondria during cell division, facilitate the transport and distribution of mitochondria, and allow the isolation of damaged organelles. Mitochondrial mobility is essential for mitochondrial distribution depending on the cellular metabolic demands...
October 16, 2018: Molecular Genetics and Metabolism
Katell Peoc'h, Hana Manceau, Zoubida Karim, Staffan Wahlin, Laurent Gouya, Hervé Puy, Jean-Charles Deybach
Porphyrias are inherited diseases with low penetrance affecting the heme biosynthesis pathway. Acute intermittent porphyria (AIP), variegate porphyria (VP) and hereditary coproporphyria (HCP) together constitute the acute hepatic porphyrias (AHP). These diseases have been identified as risk factors for primary liver cancers (PLC), mainly hepatocellular carcinoma (HCC: range 87-100%) but also cholangiocarcinoma, alone or combination with HCC. In AHP, HCC annual incidence rates range from 0.16 to 0.35% according to the populations studied...
October 9, 2018: Molecular Genetics and Metabolism
Lisa von Kleist, Khandsuren Ariunbat, Ingke Braren, Tobias Stauber, Stephan Storch, Tatyana Danyukova
Mutations in the CLN7/MFSD8 gene encoding the lysosomal membrane protein CLN7 are causative of CLN7 disease, an inherited neurodegenerative disorder that typically affects children. To gain insight into the pathomechanisms of CLN7 disease, we established an immortalized cell line based on cerebellar (Cb) granule neuron precursors isolated from Cln7-/- mice. Here, we demonstrate that Cln7-deficient neuron-derived Cb cells display an abnormal phenotype that includes increased size and defective outward movement of late endosomes and lysosomes as well as impaired lysosomal exocytosis...
October 1, 2018: Molecular Genetics and Metabolism
Dominique P Germain, Michael Arad, Alessandro Burlina, Perry M Elliott, Bruno Falissard, Ulla Feldt-Rasmussen, Max J Hilz, Derralynn A Hughes, Alberto Ortiz, Christoph Wanner, Frank Weidemann, Marco Spada
BACKGROUND: Heterozygous females with Fabry disease have a wide range of clinical phenotypes depending on the nature of their mutation and their X-chromosome inactivation pattern; it is therefore important to examine outcomes of enzyme replacement therapy (ERT) in the female patient population specifically. This paper presents the findings of a systematic literature review of treatment outcomes with ERT in adult female patients. METHODS: A comprehensive systematic literature review was conducted through January 2017 to retrieve published papers with original data on ERT in the treatment of Fabry disease...
September 27, 2018: Molecular Genetics and Metabolism
Ana Rivera-Barahona, Rosa Navarrete, Raquel García-Rodríguez, Eva Richard, Magdalena Ugarte, Celia Pérez-Cerda, Belén Pérez, Alejandra Gámez, Lourdes R Desviat
Propionic acidemia (PA) is caused by mutations in the PCCA and PCCB genes, encoding α and β subunits, respectively, of the mitochondrial enzyme propionyl-CoA carboxylase (PCC). Up to date, >200 pathogenic mutations have been identified, mostly missense defects. Genetic analysis in PA patients referred to the laboratory for the past 15 years identified 20 novel variants in the PCCA gene and 14 in the PCCB gene. 21 missense variants were predicted as probably disease-causing by different bioinformatics algorithms...
September 26, 2018: Molecular Genetics and Metabolism
Li Ou, Michael J Przybilla, Chester B Whitley
Sandhoff disease (SD) results from mutations in the HEXB gene, subsequent deficiency of N-acetyl-β-hexosaminidase (Hex) and accumulation of GM2 gangliosides. SD leads to progressive neurodegeneration and early death. However, there is a lack of established SD biomarkers, while the pathogenesis etiology remains to be elucidated. To identify potential biomarkers and unveil the pathogenic mechanisms, metabolomics analysis with reverse phase liquid chromatography (RPLC) was conducted. A total of 177, 112 and 119 metabolites were found to be significantly dysregulated in mouse liver, mouse brain and human hippocampus samples, respectively (p < ...
September 14, 2018: Molecular Genetics and Metabolism
Barbara K Burton, Kyle Bradford Jones, Stephen Cederbaum, Fran Rohr, Susan Waisbren, Debra E Irwin, Gilwan Kim, Joshua Lilienstein, Ignacio Alvarez, Elaina Jurecki, Harvey Levy
BACKGROUND: Phenylalanine hydroxylase (PAH) deficiency, otherwise known as phenylketonuria (PKU), is an inborn error of metabolism that requires treatment to be initiated in the newborn period and continued throughout life. Due to the challenges of treatment adherence and the resulting cumulative effects of high and labile blood phenylalanine, PKU exerts a significant burden of disease. Retrospective studies using large databases allow for unique perspectives on comorbidities associated with rare diseases...
September 12, 2018: Molecular Genetics and Metabolism
Laura A Adang, David B Frank, Ahmed Gilani, Asako Takanohashi, Nicole Ulrick, Abigail Collins, Zachary Cross, Csaba Galambos, Guy Helman, Usama Kanaan, Stephanie Keller, Dawn Simon, Omar Sherbini, Brian D Hanna, Adeline L Vanderver
While pulmonary hypertension (PH) is a potentially life threatening complication of many inflammatory conditions, an association between Aicardi Goutières syndrome (AGS), a rare genetic cause of interferon (IFN) overproduction, and the development of PH has not been characterized to date. We analyzed the cardiac function of individuals with AGS enrolled in the Myelin Disorders Bioregistry Project using retrospective chart review (n = 61). Additional prospective echocardiograms were obtained when possible (n = 22)...
September 7, 2018: Molecular Genetics and Metabolism
Simon Körver, Magda Vergouwe, Carla E M Hollak, Ivo N van Schaik, Mirjam Langeveld
BACKGROUND: Fabry disease (FD) is a rare lysosomal storage disorder that might result in, amongst other complications, early stroke and white matter lesions (WMLs). More insight in WMLs in FD could clarify the role of WMLs in the disease presentation and prognosis in FD. In this systematic review we assessed the prevalence, severity, location and course of WMLs in FD. We also systematically reviewed the evidence on the relation between WMLs, disease characteristics and clinical parameters...
September 5, 2018: Molecular Genetics and Metabolism
Francesca Granata, Manuel Mendez, Valentina Brancaleoni, Francisco J Castelbon, Giovanna Graziadei, Paolo Ventura, Elena Di Pierro
Genetic variants in promoters and alternative-splicing lesions require to be experimentally tested in order to validate them as causatives of a disease. The digital PCR (dPCR) approach, which is an alternative to the classical qPCR, is an innovative and a more sensitive method for the detection and quantification of nucleic acids. In the present study, we identified four HMBS gene mutations affecting the ubiquitous isoform of porphobilinogen deaminase (PBGD) and established a dPCR protocol which would be able to detect the different transcripts of this gene...
September 5, 2018: Molecular Genetics and Metabolism
Susan A Berry, Jerry Vockley, Alexander A Vinks, Min Dong, George A Diaz, Shawn E McCandless, Wendy E Smith, Cary O Harding, Roberto Zori, Can Ficicioglu, Uta Lichter-Konecki, Renee Perdok, Beth Robinson, Robert J Holt, Nicola Longo
INTRODUCTION: Glycerol phenylbutyrate (GPB) is approved in the US and EU for the chronic management of patients ≥2 months of age with urea cycle disorders (UCDs) who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. GPB is a pre-prodrug, hydrolyzed by lipases to phenylbutyric acid (PBA) that upon absorption is beta-oxidized to the active nitrogen scavenger phenylacetic acid (PAA), which is conjugated to glutamine (PAGN) and excreted as urinary PAGN (UPAGN)...
September 4, 2018: Molecular Genetics and Metabolism
Scott N Ashley, Jayme M L Nordin, Elizabeth L Buza, Jenny A Greig, James M Wilson
Argininosuccinic aciduria (ASA) is the second most common genetic disorder affecting the urea cycle. The disease is caused by deleterious mutations in the gene encoding argininosuccinate lyase (ASL); total loss of ASL activity results in severe neonatal onset of the disease, which is characterized by hyperammonemia within a few days of birth that can rapidly progress to coma and death. The long-term complications of ASA, such as hypertension and neurocognitive deficits, appear to be resistant to the current treatment options of dietary restriction, arginine supplementation, and nitrogen scavenging drugs...
August 28, 2018: Molecular Genetics and Metabolism
A Serrano Russi, S Donoghue, A Boneh, R Manara, A B Burlina, A P Burlina
Three young patients with glutaric aciduria type I (age 6-23 years) of different ethnic origins, treated for their metabolic disease since early childhood, presented with malignant central nervous system tumors. We recommend continuing clinical follow-up, including monitoring of neurological manifestations and neuroradiological findings, in all patients with glutaric aciduria type I beyond early childhood, especially if adherence to diet is poor or the treatment was not started neonatally.
August 27, 2018: Molecular Genetics and Metabolism
Steven F Dobrowolski, Irina L Tourkova, Lisa J Robinson, Cassandra Secunda, Kayla Spridik, Harry C Blair
Osteopenia is observed in some patients affected by phenylalanine hydroxylase (PAH) deficient phenylketonuria (PKU). Bone density studies, in diverse PKU patient cohorts, have demonstrated bone disease is neither fully penetrant nor uniform in bone density loss. Biochemical assessment has generated a muddled perspective regarding mechanisms of the PKU bone phenotype where the participation of hyperphenylalaninemia remains unresolved. Osteopenia is realized in the Pahenu2 mouse model of classical PKU; although, characterization is incomplete...
August 27, 2018: Molecular Genetics and Metabolism
Jaya Punetha, Loren Mackay-Loder, Tamar Harel, Zeynep Coban-Akdemir, Shalini N Jhangiani, Richard A Gibbs, Ian Lee, Deborah Terespolsky, James R Lupski, Jennifer E Posey
Charcot-Marie-Tooth (CMT) disease type 1 is an inherited peripheral neuropathy characterized by demyelination and reduced nerve conduction velocities. We present a multi-generational family with peripheral neuropathy in whom clinical CMT panel testing failed to conclude a molecular diagnosis. We found a PMP2 pathogenic variant c.155T > C, p.(Ile52Thr) that segregates with disease suggesting that PMP2 variants should be considered in patients with neuropathy and that it may be prudent to include in clinical CMT gene panels...
August 24, 2018: Molecular Genetics and Metabolism
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"