GPAT3 deficiency alleviates insulin resistance and hepatic steatosis in a mouse model of severe congenital generalized lipodystrophy.

abstract：:Niemann-Pick type C (NPC) disease, an autosomal recessive disorder caused primarily by loss-of-function mutations in NPC1 gene, is characterized neuropathologically by intracellular cholesterol accumulation, gliosis and neuronal loss in selected brain regions. Recent studies have shown that NPC disease exhibits intrig...

journal_title：Human molecular genetics

authors： Maulik M,Ghoshal B,Kim J,Wang Y,Yang J,Westaway D,Kar S

更新日期：2012-11-15 00:00:00

abstract：:Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been identified as the strongest genetic risk factors for type 2 diabetes (T2D). However, the mechanisms by which these non-coding variants increase risk for T2D are not well-established. We used 13 expression assays to survey mRNA expression of m...

journal_title：Human molecular genetics

authors： Prokunina-Olsson L,Welch C,Hansson O,Adhikari N,Scott LJ,Usher N,Tong M,Sprau A,Swift A,Bonnycastle LL,Erdos MR,He Z,Saxena R,Harmon B,Kotova O,Hoffman EP,Altshuler D,Groop L,Boehnke M,Collins FS,Hall JL

更新日期：2009-10-15 00:00:00

abstract：:Albinism is a group of genetic disorders characterized by deficient synthesis of melanin pigment. In oculocutaneous albinism (OCA) the pigment deficiency involves the skin, hair, and eyes, whereas in ocular albinism (OA) the defect involves principally the visual system. Type I (tyrosinase-deficient) OCA results from ...

journal_title：Human molecular genetics

authors： Spritz RA

更新日期：1994-01-01 00:00:00

abstract：:The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeos...

journal_title：Human molecular genetics

authors： Hannan FM,Howles SA,Rogers A,Cranston T,Gorvin CM,Babinsky VN,Reed AA,Thakker CE,Bockenhauer D,Brown RS,Connell JM,Cook J,Darzy K,Ehtisham S,Graham U,Hulse T,Hunter SJ,Izatt L,Kumar D,McKenna MJ,McKnight JA,Morr

更新日期：2015-09-15 00:00:00

abstract：:Mutations that affect calcium homeostasis (Ca(2+)) in rod photoreceptors are linked to retinal degeneration and visual disorders such as retinitis pigmentosa and congenital stationary night blindness (CSNB). It is thought that the concentration of Ca(2+) in rod outer segments is controlled by a dynamic balance between...

journal_title：Human molecular genetics

authors： Vinberg F,Wang T,Molday RS,Chen J,Kefalov VJ

更新日期：2015-10-15 00:00:00

abstract：:A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of ...

journal_title：Human molecular genetics

authors： Fisher SA,Abecasis GR,Yashar BM,Zareparsi S,Swaroop A,Iyengar SK,Klein BE,Klein R,Lee KE,Majewski J,Schultz DW,Klein ML,Seddon JM,Santangelo SL,Weeks DE,Conley YP,Mah TS,Schmidt S,Haines JL,Pericak-Vance MA,Gorin

更新日期：2005-08-01 00:00:00

abstract：:Neonatal diabetes can either remit and hence be transient or else may be permanent. These two phenotypes were considered to be genetically distinct. Abnormalities of 6q24 are the commonest cause of transient neonatal diabetes (TNDM). Mutations in KCNJ11, which encodes Kir6.2, the pore-forming subunit of the ATP-sensit...

journal_title：Human molecular genetics

authors： Gloyn AL,Reimann F,Girard C,Edghill EL,Proks P,Pearson ER,Temple IK,Mackay DJ,Shield JP,Freedenberg D,Noyes K,Ellard S,Ashcroft FM,Gribble FM,Hattersley AT

更新日期：2005-04-01 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：:PAX genes encode nuclear transcription factors which are rapidly becoming regarded as major controllers of developmental processes in both vertebrates and invertebrates. Mutations in murine Pax genes underlie three natural mouse alleles and two corresponding human syndromes. Murine Pax genes have been shown to be prot...

journal_title：Human molecular genetics

authors： Stuart ET,Gruss P

更新日期：1995-01-01 00:00:00

abstract：:Linkage, association and postmortem studies have implicated regulator of G-protein signaling 4 (RGS4), which negatively modulates signal transduction at G-protein-coupled receptors, as a candidate schizophrenia susceptibility gene. We compared RGS4 mRNA expression in the dorsolateral prefrontal cortex (DLPFC), between...

journal_title：Human molecular genetics

authors： Lipska BK,Mitkus S,Caruso M,Hyde TM,Chen J,Vakkalanka R,Straub RE,Weinberger DR,Kleinman JE

更新日期：2006-09-15 00:00:00

abstract：:Determination of variant pathogenicity represents a major challenge in the era of high-throughput sequencing. Erroneous categorization may result if variants affect genes that are in fact dispensable. We demonstrate that this also applies to rare, apparently unambiguous truncating mutations of an established disease g...

journal_title：Human molecular genetics

authors： Elsayed SM,Phillips JB,Heller R,Thoenes M,Elsobky E,Nürnberg G,Nürnberg P,Seland S,Ebermann I,Altmüller J,Thiele H,Toliat M,Körber F,Hu XJ,Wu YD,Zaki MS,Abdel-Salam G,Gleeson J,Boltshauser E,Westerfield M,Bolz HJ

更新日期：2015-05-01 00:00:00

abstract：:Friedreich ataxia (FRDA), a progressive neurodegenerative disorder associated with cardiomyopathy, is caused by severely reduced frataxin, a mitochondrial protein involved in Fe-S cluster assembly. We have recently generated mouse models that reproduce important progressive pathological and biochemical features of the...

journal_title：Human molecular genetics

authors： Seznec H,Simon D,Monassier L,Criqui-Filipe P,Gansmuller A,Rustin P,Koenig M,Puccio H

更新日期：2004-05-15 00:00:00

abstract：:Hidrotic ectodermal dysplasia (HED), Clouston type, is an autosomal dominant skin disorder which is most common in the French-Canadian population and is characterized by hair defects, nail dystrophy and palmoplantar hyperkeratosis. Biophysical and biochemical studies conducted in HED suggested a molecular abnormality ...

journal_title：Human molecular genetics

authors： Kibar Z,Der Kaloustian VM,Brais B,Hani V,Fraser FC,Rouleau GA

更新日期：1996-04-01 00:00:00

abstract：:The fragile X syndrome results from transcriptional silencing of the FMR1 gene and the absence of its encoded FMRP protein. Two autosomal homologues of the FMR1 gene, FXR1 and FXR2, have been identified and the overall structures of the corresponding proteins are very similar to that of FMRP. Using antibodies raised a...

journal_title：Human molecular genetics

authors： Khandjian EW,Bardoni B,Corbin F,Sittler A,Giroux S,Heitz D,Tremblay S,Pinset C,Montarras D,Rousseau F,Mandel J

更新日期：1998-12-01 00:00:00

abstract：:Single nucleotide polymorphisms (SNPs) that alter exon splicing efficiency are an emerging class of functional genetic variants. Since mutations in low-density lipoprotein receptor (LDLR) are a primary cause of familial hypercholesterolemia, we evaluated whether LDLR SNPs may alter splicing efficiency and cholesterol ...

journal_title：Human molecular genetics

authors： Zhu H,Tucker HM,Grear KE,Simpson JF,Manning AK,Cupples LA,Estus S

更新日期：2007-07-15 00:00:00

abstract：:Homozygous inv mice lack a functional inversin protein and exhibit situs inversus plus severe cystic changes in the kidney and pancreas. Although the inversin sequence has provided few clues to its function, we and others have previously identified calmodulin as a binding partner. We now provide evidence that inversin...

journal_title：Human molecular genetics

authors： Morgan D,Eley L,Sayer J,Strachan T,Yates LM,Craighead AS,Goodship JA

更新日期：2002-12-15 00:00:00

abstract：:The mammalian Sonic hedgehog (Shh) signalling pathway is essential for embryonic development and the patterning of multiple organs. Disruption or activation of Shh signalling leads to multiple birth defects, including holoprosencephaly, neural tube defects and polydactyly, and in adults results in tumours of the skin ...

journal_title：Human molecular genetics

authors： Patterson VL,Damrau C,Paudyal A,Reeve B,Grimes DT,Stewart ME,Williams DJ,Siggers P,Greenfield A,Murdoch JN

更新日期：2009-05-15 00:00:00

abstract：:Changes to islet cell identity in response to type 2 diabetes (T2D) have been reported in rodent models, but are less well characterized in humans. We assessed the effects of aspects of the diabetic microenvironment on hormone staining, total gene expression, splicing regulation and the alternative splicing patterns o...

journal_title：Human molecular genetics

authors： Jeffery N,Richardson S,Chambers D,Morgan NG,Harries LW

更新日期：2019-08-15 00:00:00

abstract：:Parkinson's disease (PD) is associated with olfactory defects in addition to dopaminergic degeneration. Dopaminergic signalling is necessary for subventricular zone (SVZ) proliferation and olfactory bulb (OB) neurogenesis. Alpha-synuclein (α-syn or Snca) modulates dopaminergic neurotransmission, and SNCA mutations cau...

journal_title：Human molecular genetics

authors： Zhang XM,Anwar S,Kim Y,Brown J,Comte I,Cai H,Cai NN,Wade-Martins R,Szele FG

更新日期：2019-07-15 00:00:00

abstract：:Mitochondrial dysfunction plays an important role in the etiology of neurodegenerative diseases. However, the progressive nature of neuronal loss in genetic models of mitochondrial dysfunction suggests the presence of compensatory mechanisms promoting neuronal survival under these conditions. Here, we identified the e...

journal_title：Human molecular genetics

authors： Germain M,Nguyen AP,Khacho M,Patten DA,Screaton RA,Park DS,Slack RS

更新日期：2013-03-01 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：:Slow-channel syndrome (SCS) is a congenital myasthenic disorder caused by point mutations in subunits of skeletal muscle acetylcholine receptor leading to Ca(2+) overload and degeneration of the postsynaptic membrane, nuclei and mitochondria of the neuromuscular junction (NMJ). In both SCS muscle biopsies and transgen...

journal_title：Human molecular genetics

authors： Zhu H,Pytel P,Gomez CM

更新日期：2014-01-01 00:00:00

abstract：:Polycystin-1 (PC1), encoded by the PKD1 gene that is mutated in the autosomal dominant polycystic kidney disease, regulates a number of processes including bone development. Activity of the transcription factor RunX2, which controls osteoblast differentiation, is reduced in Pkd1 mutant mice but the mechanism governing...

journal_title：Human molecular genetics

authors： Merrick D,Mistry K,Wu J,Gresko N,Baggs JE,Hogenesch JB,Sun Z,Caplan MJ

更新日期：2019-01-01 00:00:00

abstract：:An improved understanding of the expression of the cystic fibrosis gene (CFTR) will assist our approach to preventing the organ damage caused by cystic fibrosis (CF). We have studied the expression of CFTR in human fetal tissues at different gestational ages using in situ hybridization to detect CFTR mRNA. CFTR was pr...

journal_title：Human molecular genetics

authors： Tizzano EF,Chitayat D,Buchwald M

更新日期：1993-03-01 00:00:00

abstract：:Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative diseases with clinical and pathological overlap. Landmark discoveries of mutations in the transactive response DNA-binding protein (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS/TLS) as causative of A...

journal_title：Human molecular genetics

authors： Lagier-Tourenne C,Polymenidou M,Cleveland DW

更新日期：2010-04-15 00:00:00

abstract：:Gene silencing through aberrant CpG island methylation is a frequent epigenetic defect in hepatocellular carcinoma (HCC). However, nothing is known as yet whether aberrant hypermethylation occurs already in non-neoplastic liver cells from patients with hereditary haemochromatosis who have a clearly elevated risk for d...

journal_title：Human molecular genetics

authors： Lehmann U,Wingen LU,Brakensiek K,Wedemeyer H,Becker T,Heim A,Metzig K,Hasemeier B,Kreipe H,Flemming P

更新日期：2007-06-01 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：:Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar...

journal_title：Human molecular genetics

authors： Zhang L,Choi HJ,Estrada K,Leo PJ,Li J,Pei YF,Zhang Y,Lin Y,Shen H,Liu YZ,Liu Y,Zhao Y,Zhang JG,Tian Q,Wang YP,Han Y,Ran S,Hai R,Zhu XZ,Wu S,Yan H,Liu X,Yang TL,Guo Y,Zhang F,Guo YF,Chen Y,Chen X,Ta

更新日期：2014-04-01 00:00:00

abstract：:Pre-B cell leukemia factor 1 (PBX1) is an essential developmental transcription factor, mutations in which have recently been associated with CAKUTHED syndrome, characterized by multiple congenital defects including congenital heart disease (CHD). During analysis of a whole-exome-sequenced cohort of heterogeneous CHD ...

journal_title：Human molecular genetics

authors： Alankarage D,Szot JO,Pachter N,Slavotinek A,Selleri L,Shieh JT,Winlaw D,Giannoulatou E,Chapman G,Dunwoodie SL

更新日期：2020-05-08 00:00:00

abstract：:Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by a polyglutamine-encoding CAG repeat expansion in the ATXN3 gene. This expansion leads to misfolding and aggregation of mutant ataxin-3 (ATXN3) and degeneration of select brain regions. A key unanswered question in SCA3 and other polyglutami...

journal_title：Human molecular genetics

authors： Ramani B,Panwar B,Moore LR,Wang B,Huang R,Guan Y,Paulson HL

更新日期：2017-09-01 00:00:00