Great clinical variability of Nance Horan syndrome due to deleterious NHS mutations in two unrelated Spanish families

• Published in: Ophthalmic genetics 2019-11, Vol.40 (6), p.553-557
• Main Authors: Hernández, V, Pascual-Camps, I, Aparisi, M J, Martínez-Matilla, M, Martínez, F, Cerón, J A, Pedrola, L
• Format: Article
• Language: English
• ISSN: 1381-6810; 1744-5094
• DOI: 10.1080/13816810.2019.1692362

: Nance-Horan syndrome (NHS) is an X-linked rare congenital disorder caused by mutations in the gene. Clinical manifestations include congenital cataracts, facial and dental dysmorphism and, in some cases, intellectual disability. The aim of the present work was to identify the genetic cause of this disease in two unrelated Spanish NHS families and to determine the relative involvement of this gene in the pathogenesis. : Four members of a two-generation family, three males and one female (Family 1), and seven members of a three-generation family, two males and five females (Family 2) were recruited and their index cases were screened for mutations in the gene and 26 genes related with ocular congenital anomalies by NGS (Next Generation Sequencing). : Two pathogenic variants were found in the gene: a nonsense mutation (p.Arg373X) and a frameshift mutation (p.His669ProfsX5). These mutations were found in the two unrelated NHS families with different clinical manifestations. : In the present study, we identified two truncation mutations (one of them novel) in the gene, associated with NHS. Given the wide clinical variability of this syndrome, NHS may be difficult to detect in individuals with subtle clinical manifestations or when congenital cataracts are the primary clinical manifestation which makes us suspect that it can be underdiagnosed. Combination of genetic studies and clinical examinations are essential for the clinical diagnosis optimization.