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Updated: Jun 30, 2026
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Novel splice donor site mutation in MERTK gene associated with retinitis pigmentosa
A J Brea-Fernández1, E Pomares, M J Brión
1Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Fundación Galegade Medicina Xenómica (Consellería de Sanidade), Santiago de Compostela, Spain.
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.
Insights
A novel MERTK mutation (IVS16+1G>T) was identified in a Spanish family with autosomal recessive retinitis pigmentosa (arRP). This mutation disrupts MERTK gene splicing, leading to a non-functional protein crucial for retinal pigment epithelium function.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- Mutations in MERTK (MER/AXL/TYRO3 receptor kinase family) are linked to Retinal Pigment Epithelium (RPE) phagocytosis defects.
- These defects are associated with autosomal recessive retinitis pigmentosa (arRP) in humans.
Purpose of the Study:
- Report a novel MERTK mutation (IVS16+1G>T).
- Investigate the genetic cause of arRP in a Spanish consanguineous family.
Main Methods:
- Screened 21 genes using high-throughput SNP multiplexing assay.
- Performed direct sequencing of the MERTK gene, including exons and intronic boundaries.
- Confirmed the mutation's effect on mRNA splicing via cDNA analysis.
Main Results:
- Identified MERTK gene cosegregation with RP in affected family members.
- Detected a G-to-T substitution at the intron 16 splice donor site (IVS16+1G>T).
- Confirmed exon 16 skipping in the mRNA transcript due to the mutation.
Conclusions:
- The IVS16+1G>T mutation disrupts the MERTK splice donor site, causing exon 16 skipping.
- Exon 16 skipping results in a frameshift and premature termination codon, producing a non-functional MERTK protein.
- This severely impacts the tyrosine kinase domain, explaining the arRP phenotype.
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