Fischer J

References (18)

Title : High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis - Schmalz_2023_JHEP.Rep_5_100684
Author(s) : Schmalz F , Fischer J , Innes H , Buch S , Moller C , Matz-Soja M , von Schonfels W , Kramer B , Langhans B , Kluners A , Soyka M , Stickel F , Nattermann J , Strassburg CP , Berg T , Lutz P , Nischalke HD
Ref : JHEP Rep , 5 :100684 , 2023
Abstract : BACKGROUND & AIMS: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD. METHODS: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines. RESULTS: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL. CONCLUSIONS: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk. IMPACT AND IMPLICATIONS: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.
ESTHER : Schmalz_2023_JHEP.Rep_5_100684
PubMedSearch : Schmalz_2023_JHEP.Rep_5_100684
PubMedID: 36879887
Gene_locus related to this paper: human-LPL

Title : Synthesis, Biological Evaluation and Structure-Activity Relationships of Diflapolin Analogues as Dual sEH\/FLAP Inhibitors - Vieider_2019_ACS.Med.Chem.Lett_10_62
Author(s) : Vieider L , Romp E , Temml V , Fischer J , Kretzer C , Schoenthaler M , Taha A , Hernandez-Olmos V , Sturm S , Schuster D , Werz O , Garscha U , Matuszczak B
Ref : ACS Med Chem Lett , 10 :62 , 2019
Abstract : A series of derivatives of the potent dual soluble epoxide hydrolase (sEH)/5-lipoxygenase-activating protein (FLAP) inhibitor diflapolin was designed, synthesized, and characterized by (1)H NMR, (13)C NMR, and elemental analysis. These novel compounds were biologically evaluated for their inhibitory activity against sEH and FLAP. Molecular modeling tools were applied to analyze structure-activity relationships (SAR) on both targets. Results show that even small modifications on the lead compound diflapolin markedly influence the inhibitory potential, especially on FLAP, suggesting very narrow SAR.
ESTHER : Vieider_2019_ACS.Med.Chem.Lett_10_62
PubMedSearch : Vieider_2019_ACS.Med.Chem.Lett_10_62
PubMedID: 30655948

Title : Spectrum of Autosomal Recessive Congenital Ichthyosis in Scandinavia: Clinical Characteristics and Novel and Recurrent Mutations in 132 Patients - Pigg_2016_Acta.Derm.Venereol_96_932
Author(s) : Pigg MH , Bygum A , Ganemo A , Virtanen M , Brandrup F , Zimmer AD , Hotz A , Vahlquist A , Fischer J
Ref : Acta Derm Venereol , 96 :932 , 2016
Abstract : Autosomal recessive congenital ichthyosis (ARCI) represents a heterogeneous group of rare disorders of cornification with 3 major subtypes: harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). A 4th subtype has also been proposed: pleomorphic ichthyosis (PI), characterized by marked skin changes at birth and subsequently mild symptoms. In nationwide screenings of suspected cases of ARCI in Denmark and Sweden, we identified 132 patients (age range 0.1-86 years) classified as HI (n = 7), LI (n = 70), CIE (n = 17) and PI (n = 38). At birth, a collodion membrane or similar severe hyperkeratosis was reported in almost all patients with HI and LI, and in nearly half of patients with CIE and PI. Persistent ectropion was more common in HI (85%) and LI (57%), than in CIE (35%) and PI (5%). Anhidrosis was a frequent problem in all 4 groups (58-100%). A scoring (0-4) of ichthyosis/ery-thema past infancy showed widely different mean values in the subgroups: HI (3.2/3.1), LI (2.4/0.6), CIE (1.8/1.6), PI (1.1/0.3). Novel or recurrent mutations were found in 113 patients: TGM1 (n = 56), NIPAL4 (n = 15), ALOX12B (n = 15), ABCA12 (n = 8), ALOXE3 (n = 9), SLC27A4 (n = 5), CYP4F22 (n = 3), PNPLA1 (n = 1) and ABHD5 (n = 1). In conclusion, by performing a deep phenotyping and gene screening, ARCI can be definitely diagnosed in 85% of cases in Scandinavia, with a prevalence of 1:100,000 and > 8 different aetiologies.
ESTHER : Pigg_2016_Acta.Derm.Venereol_96_932
PubMedSearch : Pigg_2016_Acta.Derm.Venereol_96_932
PubMedID: 27025581
Gene_locus related to this paper: human-ABHD5

Title : The important role of epidermal triacylglycerol metabolism for maintenance of the skin permeability barrier function - Radner_2014_Biochim.Biophys.Acta_1841_409
Author(s) : Radner FP , Fischer J
Ref : Biochimica & Biophysica Acta , 1841 :409 , 2014
Abstract : Survival in a terrestrial, dry environment necessitates a permeability barrier for regulated permeation of water and electrolytes in the cornified layer of the skin (the stratum corneum) to minimize desiccation of the body. This barrier is formed during cornification and involves a cross-linking of corneocyte proteins as well as an extensive remodeling of lipids. The cleavage of precursor lipids from lamellar bodies by various hydrolytic enzymes generates ceramides, cholesterol, and non-esterified fatty acids for the extracellular lipid lamellae in the stratum corneum. However, the important role of epidermal triacylglycerol (TAG) metabolism during formation of a functional permeability barrier in the skin was only recently discovered. Humans with mutations in the ABHD5/CGI-58 (alpha/beta hydrolase domain containing protein 5, also known as comparative gene identification-58, CGI-58) gene suffer from a defect in TAG catabolism that causes neutral lipid storage disease with ichthyosis. In addition, mice with deficiencies in genes involved in TAG catabolism (Abhd5/Cgi-58 knock-out mice) or TAG synthesis (acyl-CoA:diacylglycerol acyltransferase-2, Dgat2 knock-out mice) also develop severe skin permeability barrier dysfunctions and die soon after birth due to increased dehydration. As a result of these defects in epidermal TAG metabolism, humans and mice lack omega-(O)-acylceramides, which leads to malformation of the cornified lipid envelope of the skin. In healthy skin, this epidermal structure provides an interface for the linkage of lamellar membranes with corneocyte proteins to maintain permeability barrier homeostasis. This review focuses on recent advances in the understanding of biochemical mechanisms involved in epidermal neutral lipid metabolism and the generation of a functional skin permeability barrier. This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier. Guest Editors: Kenneth R. Feingold and Peter Elias.
ESTHER : Radner_2014_Biochim.Biophys.Acta_1841_409
PubMedSearch : Radner_2014_Biochim.Biophys.Acta_1841_409
PubMedID: 23928127

Title : Development of an autism severity score for mice using Nlgn4 null mutants as a construct-valid model of heritable monogenic autism - El-Kordi_2013_Behav.Brain.Res_251_41
Author(s) : El-Kordi A , Winkler D , Hammerschmidt K , Kastner A , Krueger D , Ronnenberg A , Ritter C , Jatho J , Radyushkin K , Bourgeron T , Fischer J , Brose N , Ehrenreich H
Ref : Behavioural Brain Research , 251 :41 , 2013
Abstract : Autism is the short name of a complex and heterogeneous group of disorders (autism spectrum disorders, ASD) with several lead symptoms required for classification, including compromised social interaction, reduced verbal communication and stereotyped repetitive behaviors/restricted interests. The etiology of ASD is still unknown in most cases but monogenic heritable forms exist that have provided insights into ASD pathogenesis and have led to the notion of autism as a 'synapse disorder'. Among the most frequent monogenic causes of autism are loss-of-function mutations of the NLGN4X gene which encodes the synaptic cell adhesion protein neuroligin-4X (NLGN4X). We previously described autism-like behaviors in male Nlgn4 null mutant mice, including reduced social interaction and ultrasonic communication. Here, we extend the phenotypical characterization of Nlgn4 null mutant mice to both genders and add a series of additional autism-relevant behavioral readouts. We now report similar social interaction and ultrasonic communication deficits in females as in males. Furthermore, aggression, nest-building parameters, as well as self-grooming and circling as indicators of repetitive behaviors/stereotypies were explored in both genders. The construction of a gender-specific autism severity composite score for Nlgn4 mutant mice markedly diminishes population/sample heterogeneity typically obtained for single tests, resulting in p values of <0.00001 and a genotype predictability of 100% for male and of >83% for female mice. Taken together, these data underscore the similarity of phenotypical consequences of Nlgn4/NLGN4X loss-of-function in mouse and man, and emphasize the high relevance of Nlgn4 null mutant mice as an ASD model with both construct and face validity.
ESTHER : El-Kordi_2013_Behav.Brain.Res_251_41
PubMedSearch : El-Kordi_2013_Behav.Brain.Res_251_41
PubMedID: 23183221

Title : Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Soreze 2009 - Oji_2010_J.Am.Acad.Dermatol_63_607
Author(s) : Oji V , Tadini G , Akiyama M , Blanchet Bardon C , Bodemer C , Bourrat E , Coudiere P , DiGiovanna JJ , Elias P , Fischer J , Fleckman P , Gina M , Harper J , Hashimoto T , Hausser I , Hennies HC , Hohl D , Hovnanian A , Ishida-Yamamoto A , Jacyk WK , Leachman S , Leigh I , Mazereeuw-Hautier J , Milstone L , Morice-Picard F , Paller AS , Richard G , Schmuth M , Shimizu H , Sprecher E , Van Steensel M , Taieb A , Toro JR , Vabres P , Vahlquist A , Williams M , Traupe H
Ref : J Am Acad Dermatol , 63 :607 , 2010
Abstract : BACKGROUND: Inherited ichthyoses belong to a large, clinically and etiologically heterogeneous group of mendelian disorders of cornification, typically involving the entire integument. Over the recent years, much progress has been made defining their molecular causes. However, there is no internationally accepted classification and terminology. OBJECTIVE: We sought to establish a consensus for the nomenclature and classification of inherited ichthyoses. METHODS: The classification project started at the First World Conference on Ichthyosis in 2007. A large international network of expert clinicians, skin pathologists, and geneticists entertained an interactive dialogue over 2 years, eventually leading to the First Ichthyosis Consensus Conference held in Soreze, France, on January 23 and 24, 2009, where subcommittees on different issues proposed terminology that was debated until consensus was reached. RESULTS: It was agreed that currently the nosology should remain clinically based. "Syndromic" versus "nonsyndromic" forms provide a useful major subdivision. Several clinical terms and controversial disease names have been redefined: eg, the group caused by keratin mutations is referred to by the umbrella term, "keratinopathic ichthyosis"-under which are included epidermolytic ichthyosis, superficial epidermolytic ichthyosis, and ichthyosis Curth-Macklin. "Autosomal recessive congenital ichthyosis" is proposed as an umbrella term for the harlequin ichthyosis, lamellar ichthyosis, and the congenital ichthyosiform erythroderma group. LIMITATIONS: As more becomes known about these diseases in the future, modifications will be needed. CONCLUSION: We have achieved an international consensus for the classification of inherited ichthyosis that should be useful for all clinicians and can serve as reference point for future research.
ESTHER : Oji_2010_J.Am.Acad.Dermatol_63_607
PubMedSearch : Oji_2010_J.Am.Acad.Dermatol_63_607
PubMedID: 20643494

Title : Neuroligin-3-deficient mice: model of a monogenic heritable form of autism with an olfactory deficit - Radyushkin_2009_Genes.Brain.Behav_8_416
Author(s) : Radyushkin K , Hammerschmidt K , Boretius S , Varoqueaux F , El-Kordi A , Ronnenberg A , Winter D , Frahm J , Fischer J , Brose N , Ehrenreich H
Ref : Genes Brain Behav , 8 :416 , 2009
Abstract : Autism spectrum disorder (ASD) is a frequent neurodevelopmental disorder characterized by variable clinical severity. Core symptoms are qualitatively impaired communication and social behavior, highly restricted interests and repetitive behaviors. Although recent work on genetic mutations in ASD has shed light on the pathophysiology of the disease, classifying it essentially as a synaptopathy, no treatments are available to date. To develop and test novel ASD treatment approaches, validated and informative animal models are required. Of particular interest, in this context are loss-of-function mutations in the postsynaptic cell adhesion protein neuroligin-4 and point mutations in its homologue neuroligin-3 (NL-3) that were found to cause certain forms of monogenic heritable ASD in humans. Here, we show that NL-3-deficient mice display a behavioral phenotype reminiscent of the lead symptoms of ASD: reduced ultrasound vocalization and a lack of social novelty preference. The latter may be related to an olfactory deficiency observed in the NL-3 mutants. Interestingly, such olfactory phenotype is also present in a subgroup of human ASD patients. Tests for learning and memory showed no gross abnormalities in NL-3 mutants. Also, no alterations were found in time spent in social interaction, prepulse inhibition, seizure propensity and sucrose preference. As often seen in adult ASD patients, total brain volume of NL-3 mutant mice was slightly reduced as assessed by magnetic resonance imaging (MRI). Our findings show that the NL-3 knockout mouse represents a useful animal model for understanding pathophysiological events in monogenic heritable ASD and for developing novel treatment strategies in this devastating human disorder.
ESTHER : Radyushkin_2009_Genes.Brain.Behav_8_416
PubMedSearch : Radyushkin_2009_Genes.Brain.Behav_8_416
PubMedID: 19243448

Title : Reduced social interaction and ultrasonic communication in a mouse model of monogenic heritable autism - Jamain_2008_Proc.Natl.Acad.Sci.U.S.A_105_1710
Author(s) : Jamain S , Radyushkin K , Hammerschmidt K , Granon S , Boretius S , Varoqueaux F , Ramanantsoa N , Gallego J , Ronnenberg A , Winter D , Frahm J , Fischer J , Bourgeron T , Ehrenreich H , Brose N
Ref : Proc Natl Acad Sci U S A , 105 :1710 , 2008
Abstract : Autism spectrum conditions (ASCs) are heritable conditions characterized by impaired reciprocal social interactions, deficits in language acquisition, and repetitive and restricted behaviors and interests. In addition to more complex genetic susceptibilities, even mutation of a single gene can lead to ASC. Several such monogenic heritable ASC forms are caused by loss-of-function mutations in genes encoding regulators of synapse function in neurons, including NLGN4. We report that mice with a loss-of-function mutation in the murine NLGN4 ortholog Nlgn4, which encodes the synaptic cell adhesion protein Neuroligin-4, exhibit highly selective deficits in reciprocal social interactions and communication that are reminiscent of ASCs in humans. Our findings indicate that a protein network that regulates the maturation and function of synapses in the brain is at the core of a major ASC susceptibility pathway, and establish Neuroligin-4-deficient mice as genetic models for the exploration of the complex neurobiological disorders in ASCs.
ESTHER : Jamain_2008_Proc.Natl.Acad.Sci.U.S.A_105_1710
PubMedSearch : Jamain_2008_Proc.Natl.Acad.Sci.U.S.A_105_1710
PubMedID: 18227507
Gene_locus related to this paper: mouse-4neur

Title : The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding - Schweiger_2008_J.Biol.Chem_283_17211
Author(s) : Schweiger M , Schoiswohl G , Lass A , Radner FP , Haemmerle G , Malli R , Graier W , Cornaciu I , Oberer M , Salvayre R , Fischer J , Zechner R , Zimmermann R
Ref : Journal of Biological Chemistry , 283 :17211 , 2008
Abstract : Adipose triglyceride lipase (ATGL) catalyzes the first step in the hydrolysis of triacylglycerol (TG) generating diacylglycerol and free fatty acids. The enzyme requires the activator protein CGI-58 (or ABHD5) for full enzymatic activity. Defective ATGL function causes a recessively inherited disorder named neutral lipid storage disease that is characterized by systemic TG accumulation and myopathy. In this study, we investigated the functional defects associated with mutations in the ATGL gene that cause neutral lipid storage disease. We show that these mutations lead to the expression of either inactive enzymes localizing to lipid droplets (LDs) or enzymatically active lipases with defective LD binding. Additionally, our studies assign important regulatory functions to the C-terminal part of ATGL. Truncated mutant ATGL variants lacking approximately 220 amino acids of the C-terminal protein region do not localize to LDs. Interestingly, however, these mutants exhibit substantially increased TG hydrolase activity in vitro (up to 20-fold) compared with the wild-type enzyme, indicating that the C-terminal region suppresses enzyme activity. Protein-protein interaction studies revealed an increased binding of truncated ATGL to CGI-58, suggesting that the C-terminal part interferes with CGI-58 interaction and enzyme activation. Compared with the human enzyme, the C-terminal region of mouse ATGL is much less effective in suppressing enzyme activity, implicating species-dependent differences in enzyme regulation. Together, our results demonstrate that the C-terminal region of ATGL is essential for proper localization of the enzyme and suppresses enzyme activity.
ESTHER : Schweiger_2008_J.Biol.Chem_283_17211
PubMedSearch : Schweiger_2008_J.Biol.Chem_283_17211
PubMedID: 18445597

Title : Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease - Monti_2008_Nat.Genet_40_529
Author(s) : Monti J , Fischer J , Paskas S , Heinig M , Schulz H , Gosele C , Heuser A , Fischer R , Schmidt C , Schirdewan A , Gross V , Hummel O , Maatz H , Patone G , Saar K , Vingron M , Weldon SM , Lindpaintner K , Hammock BD , Rohde K , Dietz R , Cook SA , Schunck WH , Luft FC , Hubner N
Ref : Nat Genet , 40 :529 , 2008
Abstract : We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expression profiling and identified Ephx2 as a heart failure susceptibility gene in SHHF rats. Specifically, we found that cis variation at Ephx2 segregated with heart failure and with increased transcript expression, protein expression and enzyme activity, leading to a more rapid hydrolysis of cardioprotective epoxyeicosatrienoic acids. To confirm our results, we tested the role of Ephx2 in heart failure using knockout mice. Ephx2 gene ablation protected from pressure overload-induced heart failure and cardiac arrhythmias. We further demonstrated differential regulation of EPHX2 in human heart failure, suggesting a cross-species role for Ephx2 in this complex disease.
ESTHER : Monti_2008_Nat.Genet_40_529
PubMedSearch : Monti_2008_Nat.Genet_40_529
PubMedID: 18443590

Title : The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy - Fischer_2007_Nat.Genet_39_28
Author(s) : Fischer J , Lefevre C , Morava E , Mussini JM , Laforet P , Negre-Salvayre A , Lathrop M , Salvayre R
Ref : Nat Genet , 39 :28 , 2007
Abstract : Neutral lipid storage disease comprises a heterogeneous group of autosomal recessive disorders characterized by systemic accumulation of triglycerides in cytoplasmic droplets. Here we report a neutral lipid storage disease subgroup characterized by mild myopathy, absence of ichthyosis and mutations in both alleles of adipose triglyceride lipase (PNPLA2, also known as ATGL). Three of these mutations are predicted to lead to a truncated ATGL protein with an intact patatin domain containing the active site, but with defects in the hydrophobic domain. The block in triglyceride degradation was mimicked by short interfering RNA directed against ATGL. NLSDM is distinct from Chanarin-Dorfman syndrome, which is characterized by neutral lipid storage disease with ichthyosis, mild myopathy and hepatomegaly due to mutations in ABHD5 (also known as CGI-58).
ESTHER : Fischer_2007_Nat.Genet_39_28
PubMedSearch : Fischer_2007_Nat.Genet_39_28
PubMedID: 17187067

Title : [Neutral lipid storage diseases and ATGL (adipose triglyceride lipase) and CGI-58\/ABHD5 (alpha-beta hydrolase domain-containing 5) deficiency: myopathy, ichthyosis, but no obesity] -
Author(s) : Fischer J , Negre-Salvayre A , Salvayre R
Ref : Med Sci (Paris) , 23 :575 , 2007
PubMedID: 17631826

Title : Two new mutations of the ABHD5 gene in a new adult case of Chanarin Dorfman syndrome: an uncommon lipid storage disease -
Author(s) : Schleinitz N , Fischer J , Sanchez A , Veit V , Harle JR , Pelissier JF
Ref : Arch Dermatol , 141 :798 , 2005
PubMedID: 15967942
Gene_locus related to this paper: human-ABHD5

Title : Erythrokeratoderma variabilis-like ichthyosis in Chanarin-Dorfman syndrome - Pujol_2005_Br.J.Dermatol_153_838
Author(s) : Pujol RM , Gilaberte M , Toll A , Florensa L , Lloreta J , Gonzalez-Ensenat MA , Fischer J , Azon A
Ref : Br J Dermatol , 153 :838 , 2005
Abstract : Neutral lipid storage disease (Chanarin-Dorfman syndrome) is an autosomal recessive metabolic disorder associated with congenital ichthyosis and a multisystemic accumulation of neutral lipids (lipid droplets) in various types of cells. The clinical presentation has been reported to correspond to that of nonbullous congenital ichthyosiform erythroderma. We report a 4-year-old boy presenting a generalized ichthyosiform disorder manifested by migrating scaly plaques alternating with areas of normal-looking skin, showing erythematous borders with sharp margins, clinically suggestive of erythrokeratoderma variabilis (EKV). A peripheral blood smear revealed cytoplasmic vacuoles in most granulocytes. Genetic studies from the patient and his parents revealed that the patient carried two different and novel mutations of the ABHD5 gene: a nonsense mutation in exon 6 (transmitted by the father) and an insertion/deletion in exon 4 (transmitted by the mother). Our observation demonstrates the clinical heterogeneity of the ichthyosiform dermatoses observed in Chanarin-Dorfman syndrome and widens the clinical range of conditions presenting migrating scaly plaques mimicking EKV.
ESTHER : Pujol_2005_Br.J.Dermatol_153_838
PubMedSearch : Pujol_2005_Br.J.Dermatol_153_838
PubMedID: 16181472
Gene_locus related to this paper: human-ABHD5

Title : CGI-58\/ABHD5 gene is mutated in Dorfman-Chanarin syndrome -
Author(s) : Caux F , Selma ZB , Laroche L , Prud'homme JF , Fischer J
Ref : American Journal of Medicine Genet A , 129A :214 , 2004
PubMedID: 15316960
Gene_locus related to this paper: human-ABHD5

Title : Steatohepatitis and unsuspected micronodular cirrhosis in Dorfman-Chanarin syndrome with documented ABHD5 mutation - Srinivasan_2004_J.Pediatr_144_662
Author(s) : Srinivasan R , Hadzic N , Fischer J , Knisely AS
Ref : J Pediatr , 144 :662 , 2004
Abstract : Mutation in ABHD5 causes Dorfman-Chanarin syndrome (DCS), a multisystem triglyceride storage disorder. Ultrastructural study of leukocytes confirmed DCS in a child homozygous for a novel ABHD5 mutation, with ichthyosis, developmental delay, and steatohepatitis with cirrhosis, manifest only as elevated aminotranferase levels. We recommend early assessment for liver disease in DCS.
ESTHER : Srinivasan_2004_J.Pediatr_144_662
PubMedSearch : Srinivasan_2004_J.Pediatr_144_662
PubMedID: 15127008
Gene_locus related to this paper: human-ABHD5

Title : Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda - Chimienti_2003_Hum.Mol.Genet_12_3017
Author(s) : Chimienti F , Hogg RC , Plantard L , Lehmann C , Brakch N , Fischer J , Huber M , Bertrand D , Hohl D
Ref : Hum Mol Genet , 12 :3017 , 2003
Abstract : Mal de Meleda is an autosomal recessive inflammatory and keratotic palmoplantar skin disorder due to mutations in the ARS B gene, encoding for SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1). SLURP-1 belongs to the Ly-6/uPAR superfamily of receptor and secreted proteins, which participate in signal transduction, immune cell activation or cellular adhesion. The high degree of structural similarity between SLURP-1 and the three fingers motif of snake neurotoxins and Lynx1 suggests that this protein interacts with the neuronal acetylcholine receptors. We found that SLURP-1 potentiates the human alpha 7 nicotinic acetylcholine receptors that are present in keratinocytes. These results identify SLURP-1 as a secreted epidermal neuromodulator which is likely to be essential for both epidermal homeostasis and inhibition of TNF-alpha release by macrophages during wound healing. This explains both the hyperproliferative as well as the inflammatory clinical phenotype of Mal de Meleda.
ESTHER : Chimienti_2003_Hum.Mol.Genet_12_3017
PubMedSearch : Chimienti_2003_Hum.Mol.Genet_12_3017
PubMedID: 14506129

Title : Mutations in CGI-58, the gene encoding a new protein of the esterase\/lipase\/thioesterase subfamily, in Chanarin-Dorfman syndrome - Lefevre_2001_Am.J.Hum.Genet_69_1002
Author(s) : Lefevre C , Jobard F , Caux F , Bouadjar B , Karaduman A , Heilig R , Lakhdar H , Wollenberg A , Verret JL , Weissenbach J , Ozguc M , Lathrop M , Prud'homme JF , Fischer J
Ref : American Journal of Human Genetics , 69 :1002 , 2001
Abstract : Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive form of nonbullous congenital ichthyosiform erythroderma (NCIE) that is characterized by the presence of intracellular lipid droplets in most tissues. We previously localized a gene for a subset of NCIE to chromosome 3 (designated "the NCIE2 locus"), in six families. Lipid droplets were found in five of these six families, suggesting a diagnosis of CDS. Four additional families selected on the basis of a confirmed diagnosis of CDS also showed linkage to the NCIE2 locus. Linkage-disequilibrium analysis of these families, all from the Mediterranean basin, allowed us to refine the NCIE2 locus to an approximately 1.3-Mb region. Candidate genes from the interval were screened, and eight distinct mutations in the recently identified CGI-58 gene were found in 13 patients from these nine families. The spectrum of gene variants included insertion, deletion, splice-site, and point mutations. The CGI-58 protein belongs to a large family of proteins characterized by an alpha/beta hydrolase fold. CGI-58 contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. Interestingly, CGI-58 differs from other members of the esterase/lipase/thioesterase subfamily in that its putative catalytic triad contains an asparagine in place of the usual serine residue.
ESTHER : Lefevre_2001_Am.J.Hum.Genet_69_1002
PubMedSearch : Lefevre_2001_Am.J.Hum.Genet_69_1002
PubMedID: 11590543
Gene_locus related to this paper: human-ABHD5