{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T05:45:30Z","timestamp":1778910330718,"version":"3.51.4"},"reference-count":23,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T00:00:00Z","timestamp":1614124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Private donation","award":["Fi-201401"],"award-info":[{"award-number":["Fi-201401"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study aims to genetically characterize a two-year-old patient suffering from multiple systemic abnormalities, including skeletal, nervous and developmental involvements and Leber congenital amaurosis (LCA). Genetic screening by next-generation sequencing identified two heterozygous pathogenic variants in nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) as the molecular cause of the disease: c.439+5G&gt;T and c.299+526_*968dup.This splice variant has never been reported to date, whereas pathogenic duplication has recently been associated with cases displaying an autosomal recessive disorder that includes a severe form of spondylo-epiphyseal dysplasia, sensorineural hearing loss, intellectual disability and LCA (SHILCA), as well as some brain anomalies. Our patient presented clinical manifestations which correlated strongly with this reported syndrome. To further study the possible transcriptional alterations resulting from these mutations, mRNA expression assays were performed in the patient and her father. The obtained results detected aberrant alternative transcripts and unbalanced levels of expression, consistent with severe systemic involvement. Moreover, these analyses also detected a novel NMNAT1 isoform, which is variably expressed in healthy human tissues. Altogether, these findings represent new evidence of the correlation of NMNAT1 and SHILCA syndrome, and provide additional insights into the healthy and pathogenic expression of this gene.<\/jats:p>","DOI":"10.3390\/ijms22052262","type":"journal-article","created":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T20:53:21Z","timestamp":1614200001000},"page":"2262","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["New Insights on the Genetic Basis Underlying SHILCA Syndrome: Characterization of the NMNAT1 Pathological Alterations Due to Compound Heterozygous Mutations and Identification of a Novel Alternative Isoform"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7684-956X","authenticated-orcid":false,"given":"V\u00edctor","family":"Abad-Morales","sequence":"first","affiliation":[{"name":"Fundaci\u00f3 de Recerca de l\u2019Institut de Microcirurgia Ocular, 08035 Barcelona, Spain"},{"name":"Department of Genetics, Institut de Microcirurgia Ocular (IMO), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9426-2412","authenticated-orcid":false,"given":"Ana","family":"Wert","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 de Recerca de l\u2019Institut de Microcirurgia Ocular, 08035 Barcelona, Spain"},{"name":"Department of Pediatric Ophthalmology, Strabismus and Neurophthalmology, Institut de Microcirurgia Ocular (IMO), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda \u00c1ngeles","family":"Ruiz G\u00f3mez","sequence":"additional","affiliation":[{"name":"Pediatric Metabolic Unit and Neuropediatrics, Hospital Universitari Son Espases, 07120 Palma de Mallorca, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Navarro","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 de Recerca de l\u2019Institut de Microcirurgia Ocular, 08035 Barcelona, Spain"},{"name":"Department of Retina, Institut de Microcirurgia Ocular (IMO), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3818-3303","authenticated-orcid":false,"given":"Esther","family":"Pomares","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 de Recerca de l\u2019Institut de Microcirurgia Ocular, 08035 Barcelona, Spain"},{"name":"Department of Genetics, Institut de Microcirurgia Ocular (IMO), 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev.genet.33.1.89","article-title":"Molecular Genetics of Human Retinal Disease","volume":"33","author":"Rattner","year":"1999","journal-title":"Annu. 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