Clinical characterisation of a family with retinal dystrophy caused by mutation in the Mertk gene.
OBJECTIVE
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.
Tschernutter
M
M
Institute of Ophthalmology, Bath Street, London EC1V 9EL, UK.
Jenkins
S A
SA
Waseem
N H
NH
Saihan
Z
Z
Holder
G E
GE
Bird
A C
AC
Bhattacharya
S S
SS
Ali
R R
RR
Webster
A R
AR
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity; D058609:Visual Field Tests / Q000379:methods; D014794:Visual Fields; D000076202:c-Mer Tyrosine Kinase
D005136:Eye Proteins; D011518:Proto-Oncogene Proteins; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase