Clinical findings of end-stage retinitis pigmentosa with a homozygous PDE6A variant (p.R653X)

Kei Mizobuchi; Satoshi Katagiri; Takaaki Hayashi; Kazutoshi Yoshitake; Kaoru Fujinami; Kazuki Kuniyoshi; Reimi Mishima; Kazushige Tsunoda; Takeshi Iwata; Tadashi Nakano

doi:10.1016/j.ajoc.2018.12.019

Clinical findings of end-stage retinitis pigmentosa with a homozygous PDE6A variant (p.R653X)

Am J Ophthalmol Case Rep. 2018 Dec 19:13:110-115. doi: 10.1016/j.ajoc.2018.12.019. eCollection 2019 Mar.

Authors

Affiliations

¹ Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
² Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, Tokyo, Japan.
³ National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan.
⁴ Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Centre, Tokyo, Japan.
⁵ Department of Ophthalmology, Kindai University Faculty of Medicine, Osaka, Japan.

Abstract

Purpose: To report clinical and genetic features of a Japanese patient with end-stage retinitis pigmentosa (RP) caused by a homozygous PDE6A variant.

Methods: We performed comprehensive ophthalmic examinations. Whole exome sequencing analysis was used to investigate the RP patient with parental consanguinity. The pedigree included 4 RP patients in the two generations, which suggests presumed pseudo-autosomal dominant inheritance.

Results: A PDE6A variant (p.R653X) was identified to be homozygous and disease-causing in the patient. Homozygosity mapping revealed the homozygous region including the variant and confirmation of autosomal recessive inheritance. The patient reported night blindness at 4 years of age and exhibited typical RP fundus appearance with macula involvement during the follow-up period from at the age of 52-69 years. At the age of 52, the patient exhibited a loss of visual acuity and had severely constricted visual fields, with a further gradual deterioration of her vision until she was 69 years old. At the age of 69, funduscopy showed severe chorioretinal degeneration in the area from the posterior pole to the peripheral retina.

Conclusions and importance: This is the first report that the PDE6A variant (p.R653X) has been identified as one of the causes of autosomal recessive RP in the Japanese population. Longitudinal natural history/end-stage findings demonstrated early-onset and a severe RP phenotype with macula involvement when the patient was in her 50s and severe chorioretinal degenerations in her late 60s.

Keywords: Chorioretinal atrophy; Japanese; Next generation sequencing; PDE6A; Retinitis pigmentosa.