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Lenz, D.* ; Smith, D.E.C.* ; Crushell, E.* ; Husain, R.A.* ; Salomons, G.S.* ; Alhaddad, B.* ; Bernstein, J.A.* ; Bianzano, A.* ; Biskup, S.* ; Brennenstuhl, H.* ; Caldari, D.* ; Dikow, N.* ; Haack, T.B.* ; Hanson-Kahn, A.* ; Harting, I.* ; Horn, D.* ; Hughes, J.* ; Huijberts, M.* ; Isidor, B.* ; Kathemann, S.* ; Kopajtich, R. ; Kotzaeridou, U.* ; Küry, S.* ; Lainka, E.* ; Laugwitz, L.* ; Lupski, J.R.* ; Posey, J.E.* ; Reynolds, C.* ; Rosenfeld, J.A.* ; Schröter, J.* ; Vansenne, F.* ; Wagner, M. ; Weiß, C.* ; Wolffenbuttel, B.H.R.* ; Wortmann, S.B. ; Kölker, S.* ; Hoffmann, G.F.* ; Prokisch, H. ; Mendes, M.I.* ; Staufner, C.*

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1.

Genet. Med. 22, 1863-1873 (2020)
Verlagsversion DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Purpose Biallelic variants inLARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods Individuals with biallelic variants inLARS1were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Lars1 ; Infantile Liver Failure Syndrome Type 1 ; Acute Liver Failure ; Aminoacyl-trna Synthetase Deficiency ; Metabolic Stroke; Transfer-rna Synthetases; Recessive Mutations; Disease; Homeostasis; Mechanisms; Onset
ISSN (print) / ISBN 1530-0366
e-ISSN 1098-3600
Zeitschrift Genetics in Medicine
Quellenangaben Band: 22, Heft: 11, Seiten: 1863-1873 Artikelnummer: , Supplement: ,
Verlag Lippincott Williams & Wilkins
Verlagsort Baltimore, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
Institute of Human Genetics (IHG)
Förderungen Dietmar Hopp Foundation, St. Leon-Rot, Germany