Evolutionary redesign of the lysosomal enzyme arylsulfatase A increases efficacy of enzyme replacement therapy for metachromatic leukodystrophy.

abstract：:Human GM1-gangliosidosis is caused by a genetic deficiency of lysosomal acid beta-galactosidase (beta-gal). The disease manifests itself either as an infantile, juvenile or adult form and is primarily a neurological disorder with progressive brain dysfunction. A mouse model lacking a functional beta-gal gene has been ...

journal_title：Human molecular genetics

authors： Hahn CN,del Pilar Martin M,Schröder M,Vanier MT,Hara Y,Suzuki K,Suzuki K,d'Azzo A

更新日期：1997-02-01 00:00:00

abstract：:A significant minority of degenerative dementias lack distinctive inclusion bodies, plagues or tangles on pathological examination. Half of these cases have a positive family history of dementia. We have studied the largest published family with such a dementia and mapped the disease locus to a 12 cM region of chromos...

journal_title：Human molecular genetics

authors： Brown J,Ashworth A,Gydesen S,Sorensen A,Rossor M,Hardy J,Collinge J

更新日期：1995-09-01 00:00:00

abstract：:Mutations in both alleles of the tumour suppressor gene coding for merlin/schwannomin, an ERM family protein, cause the hereditary disease neurofibromatosis type 2 (NF2). NF2 is characterized by the development of multiple nervous system tumours especially vestibular schwannomas. Efficient oncoretrovirus-mediated gene...

journal_title：Human molecular genetics

authors： Schulze KM,Hanemann CO,Müller HW,Hanenberg H

更新日期：2002-01-01 00:00:00

abstract：:The human genome is often portrayed as consisting of three sequence types, each distinguished by their mode of evolution. Purifying selection is estimated to act on 2.5-5.0% of the genome, whereas virtually all remaining sequence is considered to have evolved neutrally and to be devoid of functionality. The third mode...

journal_title：Human molecular genetics

authors： Ponting CP,Lunter G

更新日期：2006-10-15 00:00:00

abstract：:BCS1L encodes a homolog of the Saccharomyces cerevisiae bcs1 protein, which has a known role in the assembly of Complex III of the mitochondrial respiratory chain. Phenotypes reported in association with pathogenic BCS1L variants include growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis an...

journal_title：Human molecular genetics

authors： Oláhová M,Ceccatelli Berti C,Collier JJ,Alston CL,Jameson E,Jones SA,Edwards N,He L,Chinnery PF,Horvath R,Goffrini P,Taylor RW,Sayer JA

更新日期：2019-11-15 00:00:00

abstract：:Genome editing to correct a defective β-globin gene or induce fetal globin (HbF) for patients with beta-hemoglobinopathies has the potential to be a curative strategy available to all. HbF reactivation has long been an area of intense interest given the HbF inhibition of sickle hemoglobin (HbS) polymerization. Patient...

journal_title：Human molecular genetics

authors： Demirci S,Leonard A,Tisdale JF

更新日期：2020-09-30 00:00:00

abstract：:The fields of both developmental and stem cell biology explore how functionally distinct cell types arise from a self-renewing founder population. Multipotent, proliferative human neural crest cells (hNCC) develop toward the end of the first month of pregnancy. It is assumed that most differentiate after migrating thr...

journal_title：Human molecular genetics

authors： Thomas S,Thomas M,Wincker P,Babarit C,Xu P,Speer MC,Munnich A,Lyonnet S,Vekemans M,Etchevers HC

更新日期：2008-11-01 00:00:00

abstract：:Fragile X Syndrome is the most common form of hereditary mental retardation. It is caused by a large expansion of the CGG trinucleotide repeat (>200 repeats) in the 5'-untranslated region (UTR) of the FMR1 gene that leads to silencing of its transcript. Individuals with CGG repeat expansions approximately between 60 a...

journal_title：Human molecular genetics

authors： Sofola OA,Jin P,Botas J,Nelson DL

更新日期：2007-10-01 00:00:00

abstract：:Germline mutations in the RB1 gene confer hereditary predisposition to retinoblastoma. The majority of these mutations occur de novo and differ from one patient to another. Cytogenetics and Southern blotting were shown to detect less than 15% of constitutional rearrangements. In this study we used the polymerase chain...

journal_title：Human molecular genetics

authors： Blanquet V,Turleau C,Gross MS,Goossens M,Besmond C

更新日期：1993-07-01 00:00:00

abstract：:Beckwith-Wiedemann syndrome (BWS) is an overgrowth malformation syndrome that maps to human chromosome 11p15.5, a region that harbours a number of imprinted genes. We studied the methylation status of H19 and KCNQ1OT1 (LIT1/KvDMR1) in a large series of BWS patients. Different patient groups were identified: group I pa...

journal_title：Human molecular genetics

authors： Bliek J,Maas SM,Ruijter JM,Hennekam RC,Alders M,Westerveld A,Mannens MM

更新日期：2001-03-01 00:00:00

abstract：:Mutations in the human RPGR gene cause one of the most common and severe forms of inherited retinal dystrophy, but the function of its protein product remains unclear. We have identified two genes resembling human RPGR (ZFRPGR1, ZFRPGR2) in zebrafish (Danio rerio), both of which are expressed within the nascent and ad...

journal_title：Human molecular genetics

authors： Shu X,Zeng Z,Gautier P,Lennon A,Gakovic M,Patton EE,Wright AF

更新日期：2010-02-15 00:00:00

abstract：:The tumour suppressor gene PTEN encodes a dual-specificity phosphatase that recognizes protein substrates and phosphatidylinositol-3,4,5-triphosphate. PTEN seems to play multiple roles in tumour suppression and the blockade of phosphoinositide-3-kinase signalling is important for its growth suppressive effects, althou...

journal_title：Human molecular genetics

authors： Weng LP,Smith WM,Brown JL,Eng C

更新日期：2001-03-15 00:00:00

abstract：:Peroxisome proliferator-activated receptors (PPARs) are ligand-mediated transcription factors, which control both lipid and energy metabolism and inflammation pathways. PPARγ agonists are effective in the treatment of metabolic diseases and, more recently, neurodegenerative diseases, in which they show promising neuro...

journal_title：Human molecular genetics

authors： Dumont M,Stack C,Elipenahli C,Jainuddin S,Gerges M,Starkova N,Calingasan NY,Yang L,Tampellini D,Starkov AA,Chan RB,Di Paolo G,Pujol A,Beal MF

更新日期：2012-12-01 00:00:00

abstract：:Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional...

journal_title：Human molecular genetics

authors： Fogel BL,Cho E,Wahnich A,Gao F,Becherel OJ,Wang X,Fike F,Chen L,Criscuolo C,De Michele G,Filla A,Collins A,Hahn AF,Gatti RA,Konopka G,Perlman S,Lavin MF,Geschwind DH,Coppola G

更新日期：2014-09-15 00:00:00

abstract：:Huntington's disease is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregati...

journal_title：Human molecular genetics

authors： Branco-Santos J,Herrera F,Poças GM,Pires-Afonso Y,Giorgini F,Domingos PM,Outeiro TF

更新日期：2017-10-01 00:00:00

abstract：:Glycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by mutations in the G6PC gene, encoding the catalytic subunit of glucose-6-phosphatase. Early symptoms include severe fasting intolerance, failure to thrive and hepatomegaly, biochemically associated with nonketotic hypoglycemia, fasting...

journal_title：Human molecular genetics

authors： Saeed A,Hoogerland JA,Wessel H,Heegsma J,Derks TGJ,van der Veer E,Mithieux G,Rajas F,Oosterveer MH,Faber KN

更新日期：2020-01-15 00:00:00

abstract：:Focal facial dermal dysplasia (FFDD) Type IV is a rare syndrome characterized by facial lesions resembling aplasia cutis in a preauricular distribution along the line of fusion of the maxillary and mandibular prominences. To identify the causative gene(s), exome sequencing was performed in a family with two affected s...

journal_title：Human molecular genetics

authors： Slavotinek AM,Mehrotra P,Nazarenko I,Tang PL,Lao R,Cameron D,Li B,Chu C,Chou C,Marqueling AL,Yahyavi M,Cordoro K,Frieden I,Glaser T,Prescott T,Morren MA,Devriendt K,Kwok PY,Petkovich M,Desnick RJ

更新日期：2013-02-15 00:00:00

abstract：:Glomerular disease is one of the most common causes of end-stage renal failure. Increasing evidence suggests that these glomerulopathies are frequently caused by primary lesions in the renal podocytes. One of the major consequences of podocyte lesions is the accumulation of mesangial matrix in the glomerular basement ...

journal_title：Human molecular genetics

authors： Guo JK,Menke AL,Gubler MC,Clarke AR,Harrison D,Hammes A,Hastie ND,Schedl A

更新日期：2002-03-15 00:00:00

abstract：:Genomic imprinting is a phenomenon that causes parent-origin-specific monoallelic expression of a small subset of genes, known as imprinted genes, by parentally inherited epigenetic marks. Imprinted genes at the delta-like homolog 1 gene (Dlk1)-type III iodothyronine deiodinase gene (Dio3) imprinted domain, regulated ...

journal_title：Human molecular genetics

authors： Saito T,Hara S,Kato T,Tamano M,Muramatsu A,Asahara H,Takada S

更新日期：2018-09-15 00:00:00

abstract：:Spastic paraplegia 35 (SPG35) (OMIM: 612319) or fatty acid hydroxylase-associated neurodegeneration (FAHN) is caused by deficiency of fatty acid 2-hydroxylase (FA2H). This enzyme synthesizes sphingolipids containing 2-hydroxylated fatty acids, which are particularly abundant in myelin. Fa2h-deficient (Fa2h-/-) mice de...

journal_title：Human molecular genetics

authors： Hardt R,Jordans S,Winter D,Gieselmann V,Wang-Eckhardt L,Eckhardt M

更新日期：2021-01-21 00:00:00

abstract：:Age-related macular degeneration (AMD) is a progressive neurodegenerative disease, which affects quality of life for millions of elderly individuals worldwide. AMD is associated with a diverse spectrum of clinical phenotypes, all of which include the death of photoreceptors in the central part of the human retina (cal...

journal_title：Human molecular genetics

authors： Swaroop A,Branham KE,Chen W,Abecasis G

更新日期：2007-10-15 00:00:00

abstract：:P/Q-type voltage-gated calcium channels are regulated, in part, through the cytoplasmic C-terminus of their alpha1A subunit. Genetic absence or alteration of the C-terminus leads to abnormal channel function and neurological disease. Here, we show that the terminal 60-75 kDa of the endogenous alpha1A C-terminus is cle...

journal_title：Human molecular genetics

authors： Kordasiewicz HB,Thompson RM,Clark HB,Gomez CM

更新日期：2006-05-15 00:00:00

abstract：:Fabry disease, an X-linked inborn error of glycosphingolipid catabolism, results from mutations in the alpha-galactosidase A gene at Xq22.1. To determine the nature and frequency of the molecular lesions causing the classical and milder variant Fabry phenotypes, and for precise carrier detection in Fabry families, the...

journal_title：Human molecular genetics

authors： Eng CM,Niehaus DJ,Enriquez AL,Burgert TS,Ludman MD,Desnick RJ

更新日期：1994-10-01 00:00:00

abstract：:Neonatal dried blood spots (NDBS) are a widely banked sample source that enables retrospective investigation into early life molecular events. Here, we performed low-pass whole genome bisulfite sequencing (WGBS) of 86 NDBS DNA to examine early life Down syndrome (DS) DNA methylation profiles. DS represents an example ...

journal_title：Human molecular genetics

authors： Laufer BI,Hwang H,Jianu JM,Mordaunt CE,Korf IF,Hertz-Picciotto I,LaSalle JM

更新日期：2021-01-06 00:00:00

abstract：:IGF2 loss of imprinting (LOI) is fairly prevalent and implicated in the pathogenesis of human cancer and developmental disease; however, the causes of this phenomenon are largely unknown. We determined whether the post-weaning diet of mice affects allelic expression and CpG methylation of Igf2. C57BL/6JxCast/EiJ F1 hy...

journal_title：Human molecular genetics

authors： Waterland RA,Lin JR,Smith CA,Jirtle RL

更新日期：2006-03-01 00:00:00

abstract：:Gene function in cancer can be disrupted either through genetic alterations, which directly mutate or delete genes, or epigenetic alterations, which alter the heritable state of gene expression. The latter events are mediated by formation of transcriptionally repressive chromatin states around gene transcription start...

journal_title：Human molecular genetics

authors： Baylin SB,Esteller M,Rountree MR,Bachman KE,Schuebel K,Herman JG

更新日期：2001-04-01 00:00:00

abstract：:Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association ...

journal_title：Human molecular genetics

authors： Ramirez A,van der Flier WM,Herold C,Ramonet D,Heilmann S,Lewczuk P,Popp J,Lacour A,Drichel D,Louwersheimer E,Kummer MP,Cruchaga C,Hoffmann P,Teunissen C,Holstege H,Kornhuber J,Peters O,Naj AC,Chouraki V,Bellenguez C

更新日期：2014-12-15 00:00:00

abstract：:Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in TSC1 or TSC2 resulting in hyperactivity of the mammalian target of rapamycin and disabling brain lesions. These lesions contain misplaced neurons enriched in hypoxia-inducible factor 1a (HIF1a). However, the relationship between TSC1/2 and H...

journal_title：Human molecular genetics

authors： Feliciano DM,Zhang S,Quon JL,Bordey A

更新日期：2013-05-01 00:00:00

abstract：:In vertebrates, a proneural basic helix-loop-helix transcription factor (Ath5, Atonal homolog 5) plays a crucial role in the specification of the first retinal neuron: the retinal ganglion cell (RGC). Math5 homozygous null mutant mice lack RGCs and have no optic nerve. Furthermore, the expression of the Ath5 protein i...

journal_title：Human molecular genetics

authors： Hsiung F,Moses K

更新日期：2002-05-15 00:00:00

abstract：:Genomic imprinting is a phenomenon whereby monoallelic gene expression occurs in a parent-of-origin-specific manner. A subset of imprinted genes acquires a tissue-specific imprinted status during the course of tissue development, and this process can be analyzed by means of an in vitro differentiation system utilizing...

journal_title：Human molecular genetics

authors： Kohama C,Kato H,Numata K,Hirose M,Takemasa T,Ogura A,Kiyosawa H

更新日期：2012-03-15 00:00:00