Clinical characterisation of a family with retinal dystrophy caused by mutation in the Mertk gene
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Published on: November 19, 2011
M Tschernutter1, S A Jenkins, N H Waseem
1Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK.
Background/Aim:
MERTK, a tyrosine kinase receptor protein expressed by the retinal pigment epithelium (RPE), is mutated in both rodent models and humans affected by retinal disease. This study reports a survey of families for Mertk mutations and describes the phenotype exhibited by one family.
Methods:
96 probands with retinal dystrophy, consistent with autosomal recessive segregation, were screened by direct sequencing. A family homozygous for a likely null allele was investigated clinically.
Results:
A novel frame shifting deletion was identified in one of 96 probands. Other polymorphisms were detected. The deletion allele occurred on both chromosomes of four affected family members. Electrophysiology demonstrated early loss of scotopic and macular function with later loss of photopic function. Visual acuities and visual fields were preserved into the second decade. Perception of light vision was present in a patient in the fourth decade. A "bull's eye" appearance and a hyperautofluorescent lesion at the central macula were consistent clinical findings.
Conclusions:
Mutations in Mertk are a rare cause of ARRP in humans. The study extends the phenotypic characteristics of this retinal dystrophy and shows distinctive clinical signs that may improve its clinical identification. The moderate severity and presence of autofluorescence implies that outer segment phagocytosis is not entirely absent.
Insights
Mutations in MERTK, a gene crucial for retinal health, are a rare cause of autosomal recessive retinal dystrophy. This study identifies a novel mutation and details the associated clinical features, including vision loss patterns and distinctive macular findings.
Area of Science:
- Genetics
- Ophthalmology
- Molecular Biology
Background:
- MERTK encodes a tyrosine kinase receptor essential for retinal pigment epithelium (RPE) function.
- Mutations in MERTK are implicated in various forms of retinal disease in both animal models and humans.
- This study investigates MERTK mutations in families with retinal dystrophy.
Purpose of the Study:
- To screen families with retinal dystrophy for MERTK mutations.
- To characterize the clinical phenotype associated with MERTK mutations in a human family.
- To identify novel MERTK mutations and their impact on retinal function.
Main Methods:
- Screening of 96 probands with retinal dystrophy using direct sequencing.
- Clinical investigation of a family homozygous for a MERTK null allele.
- Electrophysiological testing and ophthalmological examination.
Main Results:
- A novel frame-shifting deletion in MERTK was identified in one proband.
- The identified MERTK deletion allele was present in four affected family members.
- Clinical findings included early loss of scotopic and macular function, preserved visual acuity into the second decade, and a characteristic 'bull's eye' maculopathy with hyperautofluorescence.
Conclusions:
- MERTK mutations represent a rare cause of autosomal recessive retinal dystrophy (ARRP) in humans.
- The study expands the phenotypic spectrum of MERTK-associated retinal dystrophy, highlighting distinctive clinical signs for improved identification.
- The observed clinical severity suggests that outer segment phagocytosis is not completely abolished despite MERTK mutations.
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