DIALLO, Modibo; COURDIER, Cécile; MERCIER, Elina; SEQUEIRA, Angele; DEFAY-STINAT, Alicia; PLAISANT, Claudio; MESDAGHI, Shahram; RIGDEN, Daniel; JAVERZAT, Sophie; LASSEAUX, Eulalie; BOURGEADE, Laetitia; AUDEBERT-BELLANGER, Séverine; DOLLFUS, Hélène; HADJ-RABIA, Smail; MORICE-PICARD, Fanny; PHILIBERT, Manon; SIDIBÉ, Mohamed Kole; SMIRNOV, Vasily; SYLLA, Ousmane; MICHAUD, Vincent; ARVEILER, Benoit

doi:10.3390/ijms25168657

DIALLO, Modibo
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]

COURDIER, Cécile
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]

MERCIER, Elina
Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) [U1211 INSERM/MRGM]

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Article de revue

Ce document a été publié dans

International Journal of Molecular Sciences. 2024-08-08, vol. 25, n° 16

Résumé en anglais

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, , , , and . Rare variants (MAF < 0.01) in 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 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.< Réduire

Mots clés en anglais

Albinism

Splice variants

Exon skipping

Pseudoexon

RT-PCR

Minigene assay

URI

https://oskar-bordeaux.fr/handle/20.500.12278/202433

DOI

http://dx.doi.org/10.3390/ijms25168657

Project ANR

Approches de génétique moléculaire et fonctionnelle pour déchiffrer les mécanismes physiopathologiques de l'albinisme oculocutané.

Unités de recherche

Maladies Rares : Génétique et Métabolisme (MRGM) - UMR 1211

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Functional Characterization of Splice Variants in the Diagnosis of Albinism.