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Its inheritance mode is autosomal recessive except for one X-linked form. The molecular analysis of exonic sequences of these genes allows for about a 70% diagnostic rate. About half (15%) of the unsolved cases are heterozygous for one pathogenic or probably pathogenic variant. Assuming that the missing variant may be located in non-coding regions, we performed sequencing for 122 such heterozygous patients of either the whole genome (27 patients) or our NGS panel (95 patients) that includes, in addition to all exons of the 21 genes, the introns and flanking sequences of five genes, TYR, OCA2, SLC45A2, GPR143 and HPS1. Rare variants (MAF &lt; 0.01) in trans to the first variant were tested by RT-PCR and\/or minigene assay. Of the 14 variants tested, nine caused either exon skipping or the inclusion of a pseudoexon, allowing for the diagnosis of 11 patients. This represents 9.8% (12\/122) supplementary diagnosis for formerly unsolved patients and 75% (12\/16) of those in whom the candidate variant was in trans to the first variant. Of note, one missense variant was demonstrated to cause skipping of the exon in which it is located, thus shedding new light on its pathogenic mechanism. Searching for non-coding variants and testing them for an effect on RNA splicing is warranted in order to increase the diagnostic rate.<\/jats:p>","DOI":"10.3390\/ijms25168657","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T15:04:24Z","timestamp":1723129464000},"page":"8657","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Functional Characterization of Splice Variants in the Diagnosis of Albinism"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8884-7954","authenticated-orcid":false,"given":"Modibo","family":"Diallo","sequence":"first","affiliation":[{"name":"Laboratoire Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme, Bordeaux University, INSERM U1211, 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Courdier","sequence":"additional","affiliation":[{"name":"Laboratoire Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme, Bordeaux University, INSERM U1211, 33076 Bordeaux, France"},{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elina","family":"Mercier","sequence":"additional","affiliation":[{"name":"Laboratoire Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme, Bordeaux University, INSERM U1211, 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e8le","family":"Sequeira","sequence":"additional","affiliation":[{"name":"Laboratoire Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme, Bordeaux University, INSERM U1211, 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Defay-Stinat","sequence":"additional","affiliation":[{"name":"Laboratoire Maladies Rares, G\u00e9n\u00e9tique et M\u00e9tabolisme, Bordeaux University, INSERM U1211, 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-6717","authenticated-orcid":false,"given":"Claudio","family":"Plaisant","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique M\u00e9dicale, Centre Hospitalier Universitaire de Bordeaux, 33076 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahram","family":"Mesdaghi","sequence":"additional","affiliation":[{"name":"Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, UK"},{"name":"Computational Biology Facility, MerseyBio, University of Liverpool, Crown Street, Liverpool L69 7ZB, 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