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Lenz, D.* ; McClean, P.* ; Kansu, A.* ; Bonnen, P.E.* ; Ranucci, G.* ; Thiel, C.* ; Straub, B.K.* ; Harting, I.* ; Alhaddad, B.* ; Dimitrov, B.* ; Kotzaeridou, U.* ; Wenning, D.* ; Iorio, R.* ; Himes, R.W.* ; Kuloglu, Z.* ; Blakely, E.L.* ; Taylor, R.W.* ; Meitinger, T. ; Koelker, S.* ; Prokisch, H. ; Hoffmann, G.F.* ; Haack, T.B. ; Staufner, C.*

SCYL1 variants cause a syndrome with low gamma-glutamyl-transferase cholestasis, acute liver failure, and neurodegeneration (CALFAN).

Genet. Med. 20, 1255-1265 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Purpose: Biallelic mutations in SCYL1 were recently identified as causing a syndromal disorder characterized by peripheral neuropathy, cerebellar atrophy, ataxia, and recurrent episodes of liver failure. The occurrence of SCYL1 deficiency among patients with previously undetermined infantile cholestasis or acute liver failure has not been studied; furthermore, little is known regarding the hepatic phenotype.Methods: We aimed to identify patients with SCYL1 variants within an exome-sequencing study of individuals with infantile cholestasis or acute liver failure of unknown etiology. Deep clinical and biochemical phenotyping plus analysis of liver biopsies and functional studies on fibroblasts were performed.Results: Seven patients from five families with biallelic SCYL1 variants were identified. The main clinical phenotype was recurrent low gamma-glutamyl-transferase (GGT) cholestasis or acute liver failure with onset in infancy and a variable neurological phenotype of later onset (CALFAN syndrome). Liver crises were triggered by febrile infections and were transient, but fibrosis developed. Functional studies emphasize that SCYL1 deficiency is linked to impaired intracellular trafficking.Conclusion: SCYL1 deficiency can cause recurrent low-GGT cholestatic liver dysfunction in conjunction with a variable neurological phenotype. Like NBAS deficiency, it is a member of the emerging group of congenital disorders of intracellular trafficking causing hepatopathy.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acute Liver Failure ; Calfan Syndrome ; Congenital Disorder Of Intracellular Trafficking ; Low-ggt Cholestasis ; Scyl1; Endoplasmic-reticulum; Recessive Mutations; Golgi Homeostasis; Exome Analysis; Deficiency; Gene; Glycosylation; Disorder; Complex; Childhood
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 1530-0366
e-ISSN 1098-3600
Zeitschrift Genetics in Medicine
Quellenangaben Band: 20, Heft: 10, Seiten: 1255-1265 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Baltimore, Md.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500700-001
DOI 10.1038/gim.2017.260
WOS ID WOS:000448665700019
Scopus ID 85054024301
PubMed ID 29419818
Erfassungsdatum 2018-11-16
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