Molecular characterization of a series of 990 index patients with albinism

• Published in: Pigment cell and melanoma research 2018-07, Vol.31 (4), p.466-474
• Main Authors: Lasseaux, Eulalie, Plaisant, Claudio, Michaud, Vincent, Pennamen, Perrine, Trimouille, Aurelien, Gaston, Laetitia, Monfermé, Solène, Lacombe, Didier, Rooryck, Caroline, Morice‐Picard, Fanny, Arveiler, Benoît
• Format: Article
• Language: English
• Subjects: Albinism; Albinism - diagnosis; Albinism - genetics; Alleles; Comparative Genomic Hybridization; deletions; Diagnosis; Female; Gene Rearrangement; Gene sequencing; Genotypes; Heterogeneity; High-Throughput Nucleotide Sequencing; Humans; Hybridization; Hypoplasia; Male; Molecular chains; Molecular Diagnostic Techniques; mutations; Nerves; next‐generation sequencing; Nystagmus; Patients; Phenotypes; Pigmentation
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/pcmr.12688

Summary 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.