[HTML][HTML] Novel mutations in MERTK associated with childhood onset rod-cone dystrophy

DS Mackay, RH Henderson, PI Sergouniotis, Z Li… - Molecular …, 2010 - ncbi.nlm.nih.gov
Molecular vision, 2010ncbi.nlm.nih.gov
Purpose To report the clinical phenotype in patients with a retinal dystrophy associated with
novel mutations in the MER tyrosine kinase (MERTK) gene. Methods A consanguineous
family of Middle Eastern origin was identified, and affected members underwent a full clinical
evaluation. Linkage analysis was performed using the Affymetrix 50K chip. Regions of
homozygosity were identified. The positional candidate genes protocadherin 21 (PCDH21),
retinal G protein-coupled receptor (RGR), and MERTK were polymerase chain reaction …
Abstract
Purpose
To report the clinical phenotype in patients with a retinal dystrophy associated with novel mutations in the MER tyrosine kinase (MERTK) gene.
Methods
A consanguineous family of Middle Eastern origin was identified, and affected members underwent a full clinical evaluation. Linkage analysis was performed using the Affymetrix 50K chip. Regions of homozygosity were identified. The positional candidate genes protocadherin 21 (PCDH21), retinal G protein-coupled receptor (RGR), and MERTK were polymerase chain reaction (PCR) amplified and sequenced. Long-range PCR was performed to characterize the deletion. Two hundred and ninety-two probands with autosomal recessive, childhood onset, retinal dystrophies were analyzed using the Asper Ophthalmics Leber congenital amaurosis chip to screen for known MERTK mutations.
Results
Analysis of a 50K-Affymetrix whole genome scan identified three regions of homozygosity on chromosomes 2 and 10. Screening of the candidate gene MERTK showed a possible deletion of exon 8. Long-range PCR identified a~ 9 kb deletion within MERTK that removes exon 8. Screening of DNA from a panel of Saudi Arabian patients with autosomal recessive retinitis pigmentosa identified a second consanguineous family with the same mutation. One patient with a known MERTK mutation (p. R651X) was identified using the Asper Ophthalmics Leber congenital amaurosis chip. Further screening of the gene identified a second novel splice site mutation in intron 1. The phenotype associated with these identified MERTK mutations is of a childhood onset rod–cone dystrophy with early macular atrophy. The optical coherence tomography (OCT) appearance is distinctive with evidence of debris beneath the sensory retina.
Conclusions
Mutations in MERTK are a rare cause of retinal dystrophy. Non homologous recombination between Alu Y repeats near or within disease genes may be an important cause of retinal dystrophies.
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