Clinical and genetic characteristics of patients with KCNV2-associated cone dystrophy

Authors: Zhu Tian,  Li Hui,  Wang Lei,  Wei Xing,  Wu Shijing,  Sun Zixi,  Sui Ruifang

DOI: 10.3760/cma.j.cn115985-20200117-00030
Published 2020-04-10
Cite as Chin J Exp Ophthalmol, 2020,38(04): 312-318.

Abstract

Objective

To access the genetic defects and clinical characteristics of patients with KCNV2-associated cone dystrophy.

Methods

Three pedigrees with KCNV2-associated cone dystrophy were recruited in Peking Union Medical College Hospital from August 2017 to December 2019.Peripheral blood from each patient and their parents was collected, and genomic DNA was extracted.Targeted exome capture plus next-generation sequencing (NGS) was used to detect the candidate variants.Suspected causative variants were validated by Sanger sequencing and segregation analysis.Comprehensive ocular examinations were performed, including vision acuity, colour vision, fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), visual field and electroretinogram (ERG). This study was approved by the Institutional Review Board of Peking Union Medical College Hospital and adhered to the tenets of the Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical examination.

Results

Three probands from three unrelated Chinese families were confirmed carrying biallelic KCNV2 disease-causing variants.Two patients harbored compound heterozygous variants and one patient with history of consanguinity was identified carrying homozygous variant.Five novel variants in the KCNV2 gene were identified, including p. T121M, p.R244C, p.C199Y, p.M250R and p. L171Pfs*201.All patients enrolled in this study were male with age of 25, 16 and 2 years old, respectively.Three affected individuals complained of vision loss and photophobia and two patients demonstrated reduced color perception and nystagmus.Macular discoloration (bull’s eye maculopathy or gold foil macular reflex) was observed in fundus photographs.Macular hypofluorescence was illustrated in FAF imaging, which accompanying a broad hyperfluorescent ring surrounding the central atrophy or not.Macular thinning with loss of the inner segment ellipsoid zone was noted in OCT images, and the disruption was more profound in older patients.Central scotoma with or without peripheral visual field defects was observed in perimetry.Severe cone function loss and variable scotopic rod impairment were demonstrated in ERG, whereas a broad a-wave trough response to scotopic bright flash stimulation was noted.

Conclusions

Patients with KCNV2-associated cone dystrophy show a characteristic ERG manifestation.ERG results and KCNV2 variants in Chinese patients differ from those in foreigners.

Key words:

KCNV2 gene; Cone dystrophy; Mutation; Next-generation sequencing; Electroretinogram

Contributor Information

Zhu Tian
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Li Hui
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Wang Lei
Department of Ophthalmology, Beijing Mei’ermu Hospital, Beijing 100063, China
Wei Xing
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Wu Shijing
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Sun Zixi
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
Sui Ruifang
Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China
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Updated: May 8, 2020 — 8:37 am