Purpose: To characterize the clinical features and molecular genetic findings in a Chinese pedigree with Malattia leventinese/Doyne honeycomb retinal dystrophy.
Methods: All patients underwent ophthalmologic examinations, including Snellen best-corrected visual acuity, fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, and optical coherence tomography. Genomic DNA was isolated from blood samples. All exons of EFEMP1 were amplified by polymerase chain reaction and sequenced. Possible structural and functional impacts of the protein because of amino acid substitution were predicted by bioinformatics analysis.
Results: A heterozygous missense mutation comprising C > T in exon 10 of EFEMP1 was identified in all patients of the pedigree; this resulted in an amino acid substitution at position 345 (Arg345Trp, R345W). Clinically, six patients from the Chinese family were ascertained with varying degrees of early onset drusen. Besides the drusen, choroidal neovascularization and retinal pigment epithelium changes were noted in some patients. Increased autofluorescence corresponding to the drusen was detected in the R345W mutation patients. Intrafamilial patients with Malattia leventinese/Doyne honeycomb retinal dystrophy seem to be phenotypically variable in visual loss, ophthalmoscopic findings, autofluorescence imaging, and optical coherence tomography changes. The amino acid change may have an effect on protein structure and function through bioinformatics analysis.
Conclusion: The R345W mutation in EFEMP1 caused Malattia leventinese/Doyne honeycomb retinal dystrophy in a Chinese family. This is the first report, as per our knowledge, of the R345W mutation in EFEMP1 in a Chinese pedigree of this disease.