Disruption and therapeutic rescue of autophagy in a human neuronal model of Niemann Pick type C1.

abstract：:Autism spectrum disorder (ASD) is characterized by a triad of behavioural impairments including social behaviour. Neuroligin, a trans-synaptic adhesion molecule, has emerged as a penetrant genetic determinant of behavioural traits that signature the neuroatypical behaviours of autism. However, the function of neurolig...

journal_title：Human molecular genetics

authors： Rawsthorne H,Calahorro F,Feist E,Holden-Dye L,O'Connor V,Dillon J

更新日期：2021-01-06 00:00:00

abstract：:Adolescent idiopathic scoliosis (AIS) is a complex inherited spinal deformity whose etiology has been elusive. While common genetic variants are associated with AIS, they explain only a small portion of disease risk. To explore the role of rare variants in AIS susceptibility, exome sequence data of 391 severe AIS case...

journal_title：Human molecular genetics

authors： Haller G,Alvarado D,Mccall K,Yang P,Cruchaga C,Harms M,Goate A,Willing M,Morcuende JA,Baschal E,Miller NH,Wise C,Dobbs MB,Gurnett CA

更新日期：2016-01-01 00:00:00

abstract：:DNA methylation (DNAm) has been linked to changes in chromatin structure, gene expression and disease. The DNAm level can be affected by genetic variation; although, how this differs by CpG dinucleotide density and genic location of the DNAm site is not well understood. Moreover, the effect of disease causing variants...

journal_title：Human molecular genetics

authors： Rowlatt A,Hernández-Suárez G,Sanabria-Salas MC,Serrano-López M,Rawlik K,Hernandez-Illan E,Alenda C,Castillejo A,Soto JL,Haley CS,Tenesa A

更新日期：2016-06-15 00:00:00

abstract：:The purpose of this study was to determine whether thrombospondin (TSP)-1 promotes macrophage activity and disease progression in dysferlinopathy. First, we found that levels of TSP-1 are elevated in blood of non-ambulant dysferlinopathy patients compared with ambulant patients and healthy controls, supporting the ide...

journal_title：Human molecular genetics

authors： Urao N,Mirza RE,Corbiere TF,Hollander Z,Borchers CH,Koh TJ

更新日期：2017-12-15 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：:We have recently described the identification of a second IDS locus (IDS-2) located within 90 kb telomeric of the IDS gene (Bondeson et al. submitted). Here, we show that this region is involved in a recombination event with the IDS gene in about 13% of patients with the Hunter syndrome. Analysis of the resulting rear...

journal_title：Human molecular genetics

authors： Bondeson ML,Dahl N,Malmgren H,Kleijer WJ,Tönnesen T,Carlberg BM,Pettersson U

更新日期：1995-04-01 00:00:00

abstract：:The autosomal recessive mouse mutation retinal degeneration 6 (rd6) causes small, white retinal spots and progressive photoreceptor degeneration similar to that observed in human flecked retinal diseases. Using a positional cloning approach, we determined that rd6 mice carry a splice donor mutation in the mouse homolo...

journal_title：Human molecular genetics

authors： Kameya S,Hawes NL,Chang B,Heckenlively JR,Naggert JK,Nishina PM

更新日期：2002-08-01 00:00:00

abstract：:Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the growth of renal cysts that ultimately destroy kidney function. Mutations in the PKD1 and PKD2 genes cause ADPKD. Their protein products, polycystin-1 (PC1) and polycystin-2 (PC2) have been proposed to form a calcium-permeable receptor-channel...

journal_title：Human molecular genetics

authors： Parnell SC,Magenheimer BS,Maser RL,Pavlov TS,Havens MA,Hastings ML,Jackson SF,Ward CJ,Peterson KR,Staruschenko A,Calvet JP

更新日期：2018-10-01 00:00:00

abstract：:Protein engineering is a means to optimize protein therapeutics developed for the treatment of so far incurable diseases including cancers and genetic disorders. Here we report on an engineering approach in which we successfully increased the catalytic rate constant of an enzyme that is presently evaluated in enzyme r...

journal_title：Human molecular genetics

authors： Simonis H,Yaghootfam C,Sylvester M,Gieselmann V,Matzner U

更新日期：2019-06-01 00:00:00

abstract：:Muscle-eye-brain disease (MEB), an autosomal recessive disorder prevalent in Finland, is characterized by congenital muscular dystrophy, brain malformation and ocular abnormalities. Since the MEB phenotype overlaps substantially with those of Fukuyama-type congenital muscular dystrophy (FCMD) and Walker-Warburg syndro...

journal_title：Human molecular genetics

authors： Taniguchi K,Kobayashi K,Saito K,Yamanouchi H,Ohnuma A,Hayashi YK,Manya H,Jin DK,Lee M,Parano E,Falsaperla R,Pavone P,Van Coster R,Talim B,Steinbrecher A,Straub V,Nishino I,Topaloglu H,Voit T,Endo T,Toda T

更新日期：2003-03-01 00:00:00

abstract：:The lifetime accumulation of low-abundance, somatic mtDNA re-arrangements (sublimons) has been proposed as a potential contributor to aging, and also to diseases such as cardiomyopathy or coronary heart disease. Tissue-specific sublimons, varying in abundance by three orders of magnitude between individuals, have rece...

journal_title：Human molecular genetics

authors： Kajander OA,Karhunen PJ,Jacobs HT

更新日期：2002-02-01 00:00:00

abstract：:Immunoglobulin E (IgE) concentration in serum is elevated in atopic diseases such as asthma. A large genomic region on chromosome 5 has previously been implicated in the control of IgE levels and bronchial hyperreactivity and may, therefore, harbor genes predisposing to asthma. In an effort to confirm this linkage and...

journal_title：Human molecular genetics

authors： Laitinen T,Kauppi P,Ignatius J,Ruotsalainen T,Daly MJ,Kääriäinen H,Kruglyak L,Laitinen H,de la Chapelle A,Lander ES,Laitinen LA,Kere J

更新日期：1997-11-01 00:00:00

abstract：:Ciliary trafficking defects underlie the pathogenesis of severe human ciliopathies, including Joubert Syndrome (JBTS), Bardet-Biedl Syndrome, and some forms of retinitis pigmentosa (RP). Mutations in the ciliary protein RPGR (retinitis pigmentosa GTPase regulator) are common causes of RP-associated photoreceptor degen...

journal_title：Human molecular genetics

authors： Rao KN,Zhang W,Li L,Anand M,Khanna H

更新日期：2016-10-15 00:00:00

abstract：:The zinc metalloprotease ZMPSTE24 plays a critical role in nuclear lamin biology by cleaving the prenylated and carboxylmethylated 15-amino acid tail from the C-terminus of prelamin A to yield mature lamin A. A defect in this proteolytic event, caused by a mutation in the lamin A gene (LMNA) that eliminates the ZMPSTE...

journal_title：Human molecular genetics

authors： Barrowman J,Wiley PA,Hudon-Miller SE,Hrycyna CA,Michaelis S

更新日期：2012-09-15 00:00:00

abstract：:P-selectin is an adhesion molecule, expressed at the surface of activated cells, that mediates the interaction of activated endothelial cells or platelets with leukocytes. P-selectin expression is increased in atherosclerotic plaques, and high plasma levels of this molecule have been observed in patients with unstable...

journal_title：Human molecular genetics

authors： Herrmann SM,Ricard S,Nicaud V,Mallet C,Evans A,Ruidavets JB,Arveiler D,Luc G,Cambien F

更新日期：1998-08-01 00:00:00

abstract：:Mutations in the human ortholog of Drosophila patched (PTCH) have been identified in patients with autosomal dominant nevoid basal cell carcinoma syndrome (NBCCS), characterized by minor developmental anomalies and an increased incidence of cancers such as medulloblastoma and basal cell carcinoma. We identified many i...

journal_title：Human molecular genetics

authors： Nagao K,Togawa N,Fujii K,Uchikawa H,Kohno Y,Yamada M,Miyashita T

更新日期：2005-11-15 00:00:00

abstract：:The parent of origin-dependent expression of the IGF2 and H19 genes is controlled by the imprinting centre 1 (IC1) consisting in a methylation-sensitive chromatin insulator. Deletions removing part of IC1 have been found in patients affected by the overgrowth- and tumour-associated Beckwith-Wiedemann syndrome (BWS). T...

journal_title：Human molecular genetics

authors： Cerrato F,Sparago A,Verde G,De Crescenzo A,Citro V,Cubellis MV,Rinaldi MM,Boccuto L,Neri G,Magnani C,D'Angelo P,Collini P,Perotti D,Sebastio G,Maher ER,Riccio A

更新日期：2008-05-15 00:00:00

abstract：:A strong association between ERAP1 and ankylosing spondylitis (AS) was recently identified by the Wellcome Trust Case Control Consortium and the Australo-Anglo-American Spondylitis Consortium (WTCCC-TASC) study. ERAP1 is highly polymorphic with strong linkage disequilibrium evident across the gene. We therefore conduc...

journal_title：Human molecular genetics

authors： Harvey D,Pointon JJ,Evans DM,Karaderi T,Farrar C,Appleton LH,Sturrock RD,Stone MA,Oppermann U,Brown MA,Wordsworth BP

更新日期：2009-11-01 00:00:00

abstract：:Inherited mitochondrial optic neuropathies, such as Leber's hereditary optic neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by mutant mitochondrial proteins that lead to defects in mitochondrial complex 1-driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss. Complex 1 def...

journal_title：Human molecular genetics

authors： Yu AK,Datta S,McMackin MZ,Cortopassi GA

更新日期：2017-12-15 00:00:00

abstract：:Ether lipids (ELs), particularly plasmalogens, are essential constituents of the mammalian central nervous system. The physiological role of ELs, in vivo, however is still enigmatic. In the present study, we characterized a mouse model carrying a targeted deletion of the peroxisomal dihydroxyacetonephosphate acyltrans...

journal_title：Human molecular genetics

authors： Teigler A,Komljenovic D,Draguhn A,Gorgas K,Just WW

更新日期：2009-06-01 00:00:00

abstract：:Reduced activity of beta4-galactosyltransferase 7 (beta4GalT-7), an enzyme involved in synthesizing the glycosaminoglycan linkage region of proteoglycans, is associated with the progeroid form of Ehlers-Danlos syndrome (EDS). In the invertebrates Drosophila melanogaster and Caenorhabditis elegans, mutations in beta4Ga...

journal_title：Human molecular genetics

authors： Götte M,Spillmann D,Yip GW,Versteeg E,Echtermeyer FG,van Kuppevelt TH,Kiesel L

更新日期：2008-04-01 00:00:00

abstract：:Despite extensive progress in Huntington's disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are ...

journal_title：Human molecular genetics

authors： De Souza RA,Islam SA,McEwen LM,Mathelier A,Hill A,Mah SM,Wasserman WW,Kobor MS,Leavitt BR

更新日期：2016-05-15 00:00:00

abstract：:X-linked dyskeratosis congenita (X-DC) is caused by mutations in the housekeeping nucleolar protein dyskerin. Amino acid changes associated with X-DC are remarkably heterogeneous. Peripheral mononuclear blood cells and fibroblasts isolated from X-DC patients harbor lower steady-state telomerase RNA (TER) levels and sh...

journal_title：Human molecular genetics

authors： Zeng XL,Thumati NR,Fleisig HB,Hukezalie KR,Savage SA,Giri N,Alter BP,Wong JM

更新日期：2012-02-15 00:00:00

abstract：:Ataxia oculomotor apraxia type 1 (AOA1) is an autosomal recessive disease caused by mutations in APTX, which encodes the DNA strand-break repair protein aprataxin (APTX). CoQ10 deficiency has been identified in fibroblasts and muscle of AOA1 patients carrying the common W279X mutation, and aprataxin has been localized...

journal_title：Human molecular genetics

authors： Garcia-Diaz B,Barca E,Balreira A,Lopez LC,Tadesse S,Krishna S,Naini A,Mariotti C,Castellotti B,Quinzii CM

更新日期：2015-08-15 00:00:00

abstract：:X-linked adrenoleukodystrophy (X-ALD) is an inherited disorder characterized by axonopathy and demyelination in the central nervous system and adrenal insufficiency. Main X-ALD phenotypes are: (i) an adult adrenomyeloneuropathy (AMN) with axonopathy in spinal cords, (ii) cerebral AMN with brain demyelination (cAMN) an...

journal_title：Human molecular genetics

authors： Schlüter A,Espinosa L,Fourcade S,Galino J,López E,Ilieva E,Morató L,Asheuer M,Cook T,McLaren A,Reid J,Kelly F,Bates S,Aubourg P,Galea E,Pujol A

更新日期：2012-03-01 00:00:00

abstract：:Human gene expression traits have been shown to be dependent on gender, age and time of day in blood and other tissues. However, other factors that may impact gene expression have not been systematically explored. For example, in studies linking blood gene expression to obesity related traits, whether the fasted or fe...

journal_title：Human molecular genetics

authors： Leonardson AS,Zhu J,Chen Y,Wang K,Lamb JR,Reitman M,Emilsson V,Schadt EE

更新日期：2010-01-01 00:00:00

abstract：:We have defined unexpectedly extensive copy number variation at the human anti-microbial alpha-defensin genes DEFA1 and DEFA3, encoding human neutrophil peptides HNP-1, HNP-2 and HNP-3. There was variation in both number and position of DEFA1/DEFA3 genes in arrays of 19 kb tandem repeats on 8p23.1, so that the DEFA1 a...

journal_title：Human molecular genetics

authors： Aldred PM,Hollox EJ,Armour JA

更新日期：2005-07-15 00:00:00

abstract：:Increasing evidence suggests that the accumulation of amyloid beta (Aβ) in synapses and synaptic mitochondria causes synaptic mitochondrial failure and synaptic degeneration in Alzheimer's disease (AD). The purpose of this study was to better understand the effects of Aβ in mitochondrial activity and synaptic alterati...

journal_title：Human molecular genetics

authors： Calkins MJ,Manczak M,Mao P,Shirendeb U,Reddy PH

更新日期：2011-12-01 00:00:00

abstract：:Huntington's disease shares a common molecular basis with eight other neurodegenerative diseases, expansion of an existing polyglutamine tract. In each case, this repeat tract occurs within otherwise unrelated proteins. These proteins show widespread and overlapping patterns of expression in the brain and yet the dise...

journal_title：Human molecular genetics

authors： Henshall TL,Tucker B,Lumsden AL,Nornes S,Lardelli MT,Richards RI

更新日期：2009-12-15 00:00:00

abstract：:Peroxisomes are vital eukaryotic organelles that participate in lipid metabolism, in particular the metabolism of very-long-chain fatty acids (VLCFA). The biogenesis of peroxisomes is regulated by a set of peroxin proteins (PEX). In humans, mutations affecting peroxin protein production or function result in devastati...

journal_title：Human molecular genetics

authors： Chen H,Liu Z,Huang X

更新日期：2010-02-01 00:00:00