Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld-Rieger syndrome.
Neurogenetics
; 17(1): 17-23, 2016 Jan.
Article
en En
| MEDLINE
| ID: mdl-26489929
ABSTRACT
Axenfeld-Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye, often leading to secondary glaucoma and several systemic malformations. It is inherited in an autosomal dominant fashion that has been associated with genetic defects in PITX2 and FOXC1. Known genes CYP1b1, PITX2, and FOXC1 were excluded by Sanger sequencing. The purpose of current study is to identify the underlying genetic causes in ARS family by whole exome sequencing (WES). WES was performed for affected proband of family, and variants were prioritized based on in silico analyses. Segregation analysis of candidate variants was performed in family members. A novel heterozygous PRDM5 missense variant (c.877A>G; p.Lys293Glu) was found to segregate with the disease in an autosomal dominant fashion. The novel missense variant was absent from population-matched controls, the Exome Variant Server, and an in-house exome variant database. The Lys293Glu variant is predicted to be pathogenic and affects a lysine residue that is conserved in different species. Variants in the PRDM5 gene were previously identified in anterior segment defects, i.e., autosomal recessive brittle cornea syndrome and keratoconus. The results of this study suggest that genetic variants in PRDM5 can lead to various syndromic and nonsyndromic disorders affecting the anterior segment of the eye.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Anomalías del Ojo
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Mutación Missense
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Proteínas de Unión al ADN
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Segmento Anterior del Ojo
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Neurogenetics
Asunto de la revista:
GENETICA
/
NEUROLOGIA
Año:
2016
Tipo del documento:
Article