1. Molecular characterization of a series of 990 index patients with albinism
- Author
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Vincent Michaud, Claudio Plaisant, Caroline Rooryck, Fanny Morice-Picard, Eulalie Lasseaux, Didier Lacombe, Benoit Arveiler, Laetitia Gaston, Perrine Pennamen, Aurélien Trimouille, and Solene Monfermé
- Subjects
Male ,0301 basic medicine ,Albinism ,Dermatology ,Disease ,Biology ,General Biochemistry, Genetics and Molecular Biology ,DNA sequencing ,03 medical and health sciences ,medicine ,Humans ,Allele ,Alleles ,Hypopigmentation ,Gene Rearrangement ,Genetics ,Comparative Genomic Hybridization ,Genetic heterogeneity ,High-Throughput Nucleotide Sequencing ,medicine.disease ,Hypoplasia ,030104 developmental biology ,Molecular Diagnostic Techniques ,Oncology ,Female ,medicine.symptom ,Comparative genomic hybridization - Abstract
Albinism is a clinically and genetically heterogeneous disease characterized by variable degrees of hypopigmentation and by nystagmus, foveal hypoplasia, and chiasmatic misrouting of the optic nerves. The wide phenotypic heterogeneity impedes the establishment of phenotype-genotype correlations. To obtain a precise diagnosis, we screened the 19 known albinism genes in 990 index patients using targeted next-generation sequencing (NGS) and high-resolution comparative genomic hybridization. A molecular diagnosis was obtained in 72.32% of patients. A total of 243 new pathogenic variants were identified. Intragenic rearrangements represented 10.8% of all pathogenic alleles. NGS panel analysis allowed establishing a diagnosis for the rarest forms of the disease, which could not be diagnosed otherwise. Because of the clinical overlap between the different forms of the disease, diagnosis nowadays clearly relies on molecular grounds.
- Published
- 2018