{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:16:32Z","timestamp":1791288992907,"version":"4.3.0"},"reference-count":38,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T00:00:00Z","timestamp":1621814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gaucher disease (GD) is an autosomal recessive lysosomal disorder due to beta-glucosidase gene (GBA) mutations. The molecular diagnosis of GD is complicated by the presence of recombinant alleles originating from a highly homologous pseudogene. Clinical exome sequencing (CES) is a rapid genetic approach for identifying disease-causing mutations. However, copy number variation and recombination events are poorly detected, and further investigations are required to avoid mis-genotyping. The aim of this work was to set-up an integrated strategy for GD patients genotyping using CES as a first-line test. Eight patients diagnosed with GD were analyzed by CES. Five patients were fully genotyped, while three were revealed to be homozygous for mutations that were not confirmed in the parents. Therefore, MLPA (multiplex ligation-dependent probe amplification) and specific long-range PCR were performed, and two recombinant alleles, one of them novel, and one large deletion were identified. Furthermore, an MLPA assay performed in one family resulted in the identification of an additional novel mutation (p.M124V) in a relative, in trans with the known p.N409S mutation. In conclusion, even though CES has become extensively used in clinical practice, our study emphasizes the importance of a comprehensive molecular strategy to provide proper GBA genotyping and genetic counseling.<\/jats:p>","DOI":"10.3390\/ijms22115538","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T12:38:01Z","timestamp":1621859881000},"page":"5538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Accurate Molecular Diagnosis of Gaucher Disease Using Clinical Exome Sequencing as a First-Tier Test"],"prefix":"10.3390","volume":"22","author":[{"given":"Stefania","family":"Zampieri","sequence":"first","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Cattarossi","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Pavan","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4660-821X","authenticated-orcid":false,"given":"Antonio","family":"Barbato","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, Federico II University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Fiumara","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Regional Referral Center for Inherited Metabolic Disease, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Peruzzo","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Ciana","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Dardis","sequence":"additional","affiliation":[{"name":"Regional Coordinator Centre for Rare Diseases, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,24]]},"reference":[{"key":"ref_1","unstructured":"Scriver, C.R., Beaudet, A.L., Valle, D., and Sly, W.S. 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