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

Genetics in Medicine : Official Journal of the American College of Medical Genetics
Dominic LenzChristian Staufner

Abstract

Biallelic variants in LARS1, 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. Individuals with biallelic variants in LARS1 were 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. 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. ILFS1 is characterized by recurrent elevation of liver transamina...Continue Reading

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Citations

Apr 18, 2021·Scientific Reports·Masanori InoueToshikatsu Hanada
Jun 20, 2021·Journal of Inherited Metabolic Disease·Heiko BrennenstuhlUNKNOWN Unified Registry for Inherited Metabolic Disorders (U-IMD) Consortium and the European Registry for Hereditary Metabolic Dis
Aug 28, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Guy HelmanRalf A Husain

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Methods Mentioned

BETA
exome sequencing
aminoacylation
SGA
biopsy
biopsies

Software Mentioned

PolyPhen
RStudio
CADD
REVEL
ggplot2
Mutalyzer Position
SPSS
SIFT
Ensembl
CAP

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