Phenylalanyl-tRNA synthetase deficiency caused by biallelic variants in FARSA gene and literature review.
Exome sequencing
FARSA gene
FARSA-deficiency
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
13 10 2023
13 10 2023
Historique:
received:
15
05
2023
accepted:
13
09
2023
medline:
1
11
2023
pubmed:
14
10
2023
entrez:
13
10
2023
Statut:
epublish
Résumé
Aminoacyl-tRNA synthetases (ARSs) are indispensable enzymes for protein biosynthesis in cells. The phenylalanyl-tRNA synthetase (FARS1) located in cytoplasm which consists of two FARS alpha subunits (FARSA) and two FARS beta subunits (FARSB). Autosomal recessive inheritance of pathogenic variants of FARSA or FARSB can result in defective FARS1 which are characterized by interstitial lung disease, liver disease, brain abnormalities, facial dysmorphism and growth restriction. Exome sequencing was used to detect the candidate variants. The in silico prediction and expressional level analysis were performed to evaluate the pathogenicity of the variations. Additionally, we presented the patient's detailed clinical information and compared the clinical feature with other previously reported patients with FARSA-deficiency. We identified compound heterozygous rare missense variants (c.1172 T > C/ p.Leu391Pro and c.1211G > A/ p.Arg404His) in FARSA gene in a Chinese male patient. The protein structure prediction and the analysis of levels of FARSA and FARSB subunits indicated both variants pathogenic. Clinical feature review indicated inflammatory symptoms in young infants may be an additional key feature. Thyroid dysfunction should be considered as a phenotype with variable penetrance. Our results expanded the current phenotypic and genetic spectrum of FARSA-deficiency.
Sections du résumé
BACKGROUND
Aminoacyl-tRNA synthetases (ARSs) are indispensable enzymes for protein biosynthesis in cells. The phenylalanyl-tRNA synthetase (FARS1) located in cytoplasm which consists of two FARS alpha subunits (FARSA) and two FARS beta subunits (FARSB). Autosomal recessive inheritance of pathogenic variants of FARSA or FARSB can result in defective FARS1 which are characterized by interstitial lung disease, liver disease, brain abnormalities, facial dysmorphism and growth restriction.
METHODS
Exome sequencing was used to detect the candidate variants. The in silico prediction and expressional level analysis were performed to evaluate the pathogenicity of the variations. Additionally, we presented the patient's detailed clinical information and compared the clinical feature with other previously reported patients with FARSA-deficiency.
RESULTS
We identified compound heterozygous rare missense variants (c.1172 T > C/ p.Leu391Pro and c.1211G > A/ p.Arg404His) in FARSA gene in a Chinese male patient. The protein structure prediction and the analysis of levels of FARSA and FARSB subunits indicated both variants pathogenic. Clinical feature review indicated inflammatory symptoms in young infants may be an additional key feature. Thyroid dysfunction should be considered as a phenotype with variable penetrance.
CONCLUSIONS
Our results expanded the current phenotypic and genetic spectrum of FARSA-deficiency.
Identifiants
pubmed: 37833669
doi: 10.1186/s12920-023-01662-0
pii: 10.1186/s12920-023-01662-0
pmc: PMC10571242
doi:
Substances chimiques
Phenylalanine-tRNA Ligase
EC 6.1.1.20
Amino Acyl-tRNA Synthetases
EC 6.1.1.-
Types de publication
Review
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
245Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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