Author: Kiyoko Gocho (France)
Co-authors: Daiki Kubota, Kaori Matsumoto, Mika Hayashi, Noriko Oishi, Hiroshi Takahashi, Shuhei Kameya
Purpose
The hexokinase 1 (HK1) gene encodes one of the four human hexokinases that play essential roles in glucose metabolism. Recently, several cases of E847K mutation in the HK1 gene were reported to cause inherited retinal dystrophy. The purpose of this study was to identify the phenotypical characteristics of patients with a recurrent E847K mutation in the HK1 gene.
Setting/Venue
All subjects were recruited and examined at a university hospital, the Nippon Medical School Chiba Hokusoh hospital in Japan. The procedures used in this study conformed to the tenets of the Declaration of Helsinki, and they were approved by the Institutional Review Board of the Nippon Medical School. A signed written informed consent was obtained from the patient and family members after the nature and possible consequences of the study were explained.
Methods
Three generations of one family with autosomal dominant retinitis pigmentosa were examined. Whole exome sequencing was performed on the DNA. The ophthalmological examinations included measurements of the best-corrected visual acuity (BCVA), slit-lamp bio-microscopy, ophthalmoscopy, Goldman kinetic perimetry, fundus photography, fundus auto-fluorescence imaging (FAF) with short-wavelength excitation, spectral domain optical coherence tomography (SD-OCT), full-field electroretinography (ERG), and multifocal ERGs (mfERGs). The ERGs were recorded using the extended testing proto-col conforming to the International Society for Clinical Electrophysiology of Vision protocol (ISCEV). Fundus imaging by an adaptive optics fundus camera was used to obtain high-resolution photoreceptor images, and cone densities of the families were compared to that of normal eyes of healthy subjects.
Results
Fundus examination of the proband showed degeneration of the mid-peripheral retina, and SD- OCT images showed an absence of the ellipsoid zone (EZ) and interdigitation zone (IZ) in the parafovea and more peripherally. SD-OCT images of the mother of the proband showed an absence of the EZ and IZ, and fundus autofluorescence images showed hypo-autofluorescence surrounding the macular region. One daughter of the proband had only mild night blindness, however, the density of the cone photo-receptors was reduced in the parafoveal region. Whole exome sequencing identified a heterozygous variant, E847K, in the HK1 gene. This variant was found to co-segregate with the disease in three family members.
Conlusions
Fundus, FAF, and OCT imaging revealed that the areas of photoreceptor degeneration were mainly in the parafovea to mid-peripheral region. High-resolution retinal imaging by AO revealed that the cone photoreceptor densities were significantly reduced in the parafoveal area at the age of 20 years, though fundus examinations showed only slight abnormalities without functional visual defects at this age. High-resolution retinal imaging analysis, such as that by AO and FAF analysis would be helpful in identifying patients with HK1-retinopathy caused by an E847K mutation. AO examination in between the different generations might be helpful to understand the prognosis and progression of the diseases.
Financial Disclosure
Kiyoko GOCHO（spouse）：imagine eyes
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