{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:41:02Z","timestamp":1784889662144,"version":"3.55.0"},"reference-count":18,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: The FARSA gene encodes for the catalytic \u03b1 subunit of Cytoplasmic phenylalanine-tRNA synthetase (FARS1), an essential enzyme for protein biosynthesis in transferring its amino acid component to tRNAs. Biallelic pathogenic variants have been associated with a multisystemic condition, characterized by variable expressivity and incomplete penetrance. Here, we report the case of an 11 year-old girl presenting interstitial lung disease, supratentorial leukoencephalopathy with brain cysts, hepatic dysfunction, hypoalbuminemia, skin and joint hyperlaxity, growth retardation, and dysmorphic features. In addition, our patient also developed two clinical features never reported before: hypergammaglobulinemia and myopic chorioretinitis. Methods: NGS analysis of the patient\u2019s skin-derived DNA revealed two novel biallelic variants in FARSA gene (NM_004461.3) never described before: the maternal nonsense variant, c.799C&gt;T [p.(Gln267Ter)], and the paternal missense variant, c.737T&gt;C [p.(Met246Thr)], both predicted as deleterious. Results: From a therapeutic perspective, this young girl has been enrolled in a clinical trial with Nintedanib, in order to treat the severe pulmonary fibrosis, with interesting initial results. Conclusions: Our findings expand the clinical and molecular spectrum of the FARSA-related phenotype and introduce new cues on lung fibrosis treatment in pediatric age.<\/jats:p>","DOI":"10.3390\/genes15121573","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T03:44:47Z","timestamp":1733456687000},"page":"1573","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Two Novel Biallelic Variants in the FARSA Gene: The First Italian Case and a Literature Review"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5510-6737","authenticated-orcid":false,"given":"Sonia","family":"Lomuscio","sequence":"first","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Medical Genetics Unit, Tor Vergata University Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8583-3866","authenticated-orcid":false,"given":"Dario","family":"Cocciadiferro","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9478-7929","authenticated-orcid":false,"given":"Francesco","family":"Petrizzelli","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza, 71013 S. Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niccol\u00f2","family":"Liorni","sequence":"additional","affiliation":[{"name":"Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza, 71013 S. Giovanni Rotondo, Italy"},{"name":"Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0434-8533","authenticated-orcid":false,"given":"Tommaso","family":"Mazza","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"},{"name":"Laboratory of Bioinformatics, IRCCS Casa Sollievo della Sofferenza, 71013 S. Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4685-7205","authenticated-orcid":false,"given":"Annalisa","family":"Allegorico","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Pneumology and UTSIR, Santobono-Pausillipon Hospital, 80129 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1111-5690","authenticated-orcid":false,"given":"Nicola","family":"Ullmann","sequence":"additional","affiliation":[{"name":"Paediatric Pulmonology and Cystic Fibrosis Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-602X","authenticated-orcid":false,"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[{"name":"Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Medical Genetics Unit, Tor Vergata University Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7711-5672","authenticated-orcid":false,"given":"Renato","family":"Cutrera","sequence":"additional","affiliation":[{"name":"Paediatric Pulmonology and Cystic Fibrosis Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1111\/cge.13943","article-title":"FARS1-related disorders caused by bi-allelic mutations in cytosolic phenylalanyl-tRNA synthetase genes: Look beyond the lungs!","volume":"99","author":"Schuch","year":"2021","journal-title":"Clin. 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Rare Dis."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/12\/1573\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:48:06Z","timestamp":1760114886000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/12\/1573"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,5]]},"references-count":18,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["genes15121573"],"URL":"https:\/\/doi.org\/10.3390\/genes15121573","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,5]]}}}