ORIGINAL ARTICLES

Novel splice donor site mutation in MERTK gene associated with retinitis pigmentosa

A J Brea-Fernández^1,2, E Pomares^2,3,4, M J Brión^1,2, G Marfany^2,3,4, M J Blanco⁵, M Sánchez-Salorio⁶, R González-Duarte^2,3,4 and A Carracedo^1,2

¹ Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Fundación Galega de Medicina Xenómica (Consellería de Sanidade), Santiago de Compostela, Spain
² Centre for Biomedical Research on Rare Diseases (CIBERER), Instituto Carlos III, Spain
³ Departament de Genètica, Facultat de Biología, Universitat de Barcelona, Barcelona, Spain
⁴ Institut de Biomedicina de la Universitat de Barcelona (IBUB), Barcelona, Spain
⁵ Servicio de Oftamoloxía, Complexo Hospitalario Universitario de Santiago, Spain
⁶ Fundación Instituto Galego de Oftalmoloxía (Consellería de Sanidade), Santiago de Compostela, Spain

Correspondence to:
Dr Á Carracedo, Grupo de Investigación de Medicina Xenómica, Fundación Galega de Medicina Xenómica, Choupana s/n, E-15706 Santiago de Compostela, Spain; apimlang{at}usc.es

Background/aim: Mutations in MERTK, a member of the MER/AXL/TYRO3 receptor kinase family, have been associated with disruption of the Retinal Pigment Epithelium (RPE) phagocytosis pathway and settling of autosomal recessive RP (arRP) in humans. This study reports a novel MERTK mutation (IVS16+1G>T) in a Spanish consanguineous family presenting arRP.

Methods: 21 genes were screened by high-throughput SNP multiplexing assay. Subsequent direct sequencing was performed in exons and intronic boundaries of the cosegregating gene. The effect of the mutation in mRNA splicing was confirmed by cDNA analysis.

Results: Haplotypic data revealed MERTK cosegregation with RP in affected individuals. MERTK sequencing showed a G-to-T substitution at the first nucleotide of intron 16. Finally, cDNA analysis confirmed the lack of exon 16 in the mRNA splicing process.

Conclusions: IVS16+1G>T disrupts the splice donor site causing exon 16 skipping. Absence of exon 16 causes a frameshift and, subsequently, the introduction of a premature termination codon into exon 17 creating an altered mRNA transcript with a seriously affected tyrosine kinase domain.

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