دورية أكاديمية
Functional Characterization of Splice Variants in the Diagnosis of Albinism
العنوان: | Functional Characterization of Splice Variants in the Diagnosis of Albinism |
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المؤلفون: | Modibo Diallo, Cécile Courdier, Elina Mercier, Angèle Sequeira, Alicia Defay-Stinat, Claudio Plaisant, Shahram Mesdaghi, Daniel Rigden, Sophie Javerzat, Eulalie Lasseaux, Laetitia Bourgeade, Séverine Audebert-Bellanger, Hélène Dollfus, Smail Hadj-Rabia, Fanny Morice-Picard, Manon Philibert, Mohamed Kole Sidibé, Vasily Smirnov, Ousmane Sylla, Vincent Michaud, Benoit Arveiler |
المصدر: | International Journal of Molecular Sciences, Vol 25, Iss 16, p 8657 (2024) |
بيانات النشر: | MDPI AG, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | albinism, splice variants, exon skipping, pseudoexon, RT-PCR, minigene assay, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | Albinism is a genetically heterogeneous disease in which 21 genes are known so far. 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 < 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. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 25168657 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/25/16/8657; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms25168657 |
URL الوصول: | https://doaj.org/article/dcc5dff4ddd3427182d939adf32a6058 |
رقم الأكسشن: | edsdoj.5dff4ddd3427182d939adf32a6058 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 25168657 14220067 16616596 |
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DOI: | 10.3390/ijms25168657 |