Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pathogenic variants in genes encoding aminoacyl-tRNA synthetases cause numerous disorders characterized by involvement of neurons, muscles, lungs and liver. Recently, biallelic FARSB defects have been shown to cause severe growth restriction with combined brain, liver and lung involvement (Rajab interstitial lung disease [ILD] with brain calcifications). Herein, for the first time, we present a patient with similar condition associated with biallelic mutations in FARSA (NM_004461.3: c.766T>C:p.Phe256Leu and c.1230C>A:p.Asn410Lys). Both detected FARSA variants are ultrarare and predicted to be damaging by in silico programs. Furthermore, they are both located in the active site of phenylalanyl-tRNA synthetase (PheRS) with Asn410Lys directly affecting a residue forming the wall of the phenylalanine-binding pocket. Clinical features shared between our patient and the FARSB syndrome include ILD with cholesterol pneumonitis, growth delay, hypotonia, brain calcifications with cysts and liver dysfunction. Our findings indicate that a disease similar to a syndrome associated with FARSB defects can also be caused by biallelic FARSA mutations. These findings are consistent with molecular structure of PheRS which is a tetramer including both FARSA and FARSB proteins.
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PMID:FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by FARSB defects. 3135 8