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

Fecha de publicación: 01/12/2019 Fecha Ahead of Print: 22/11/2019

Autores de IIS La Fe

Vicente Hernandez Garcia

Autor
Isabel Pascual Camps

Autor
Maria Jose Aparisi Navarro

Autor
Marina Martinez Matilla

Autor
Francisco Martínez Castellano

Autor
Juan Antonio Ceron Perez

Autor
Laia Pedrola Vidal

Autor

Grupos

Investigación Traslacional en Genética

Leader

Francisco Martínez Castellano
Perinatología

Leader

Máximo Vento Torres

Abstract

Background : Nance-Horan syndrome (NHS) is an X-linked rare congenital disorder caused by mutations in the NHS 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. Materials and methods : 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 NHS gene and 26 genes related with ocular congenital anomalies by NGS (Next Generation Sequencing). Results : Two pathogenic variants were found in the NHS 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. Conclusions : In the present study, we identified two truncation mutations (one of them novel) in the NHS 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.

Datos de la publicación

ISSN/ISSNe:: 1381-6810, 1744-5094
Tipo:: Article
Páginas:: 1-5
DOI:: 10.1080/13816810.2019.1692362
Factor de Impacto:: 0,626 SCImago ℠
Cuartil:: Q2 SCImago ℠

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Filiaciones

Hernández V:: Genetics Unit, La Fe University and Polytechnic Hospital, Valencia, Spain
Pascual-Camps I:: Department of Ophthalmology, La Fe University and Polytechnic Hospital, Valencia, Spain
Aparisi MJ:: Instituto de Investigación. Genomic Unit, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
Martínez-Matilla M:: Instituto de Investigación. Genomic Unit, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
Martínez F:: Genetics Unit, La Fe University and Polytechnic Hospital, Valencia, Spain

Instituto de Investigación. Genomic Unit, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain
Cerón JA:: Genetics Unit, La Fe University and Polytechnic Hospital, Valencia, Spain
Pedrola L:: Instituto de Investigación. Genomic Unit, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain