A novel haplotype with the R345W mutation in the EFEMP1 gene associated with autosomal dominant drusen in a Japanese family.
OBJECTIVE
To describe ophthalmic and molecular genetic findings in a family of Japanese patients with Malattia leventinese (ML)/Doyne honeycomb retinal dystrophy (DHRD), also known as autosomal dominant drusen.


METHODS
Four patients with ML/DHRD, including a 42-year-old female proband, were ascertained. The proband underwent complete ophthalmic examinations, including fundus and electrodiagnostic investigations, and Humphrey visual field (VF) perimetry. Mutation screening of the EFEMP1 gene and haplotype analysis were performed in the family, an Indian ML/DHRD family, and a branch of 1 of 39 ML/DHRD families in the United States, in which all affected patients shared a common haplotype.


RESULTS
A heterozygous missense mutation (p.R345W) was identified in all four Japanese patients and in affected patients of the other two families. This mutation was the only mutation that has been exclusively found in the gene. The disease haplotype in the Japanese family was different from those of the other two families. Clinically, central retinas were prominently affected in the proband and her mother, and subsequently the proband developed subfoveal choroidal neovascularization in the left eye, whereas her younger sister with the mutation, who was asymptomatic, exhibited only fine macular drusen. Long-term follow-up of Humphrey VF and multifocal-electroretinography (mfERG) in the proband also revealed progressive attenuation of macular function in the right eye.


CONCLUSIONS
This is the first report to describe a Japanese family with variable expressivity of ML/DHRD, in which a novel disease haplotype was identified. Humphrey VF and mfERG testing may be helpful in determining the long-term outcome of macular function.
Takeuchi
Tomokazu
T
Department of Ophthalmology, he Jikei University School of Medicine, Tokyo, Japan. taka@jikei.ac.jp
Hayashi
Takaaki
T
Bedell
Matthew
M
Zhang
Kang
K
Yamada
Hisashi
H
Tsuneoka
Hiroshi
H
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D004252:DNA Mutational Analysis; D004585:Electrooculography; D004596:Electroretinography; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005799:Genes, Dominant; D006239:Haplotypes; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D015593:Retinal Drusen / Q000175:diagnosis / Q000235:genetics*; D014794:Visual Fields
C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins