Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings

• Main Authors: Kei Mizobuchi, Takaaki Hayashi, Kazutoshi Yoshitake, Kaoru Fujinami, Toshiaki Tachibana, Kazushige Tsunoda, Takeshi Iwata, Tadashi Nakano
• Format: Article
• Language: English
• Published: Wiley 2020-08-01
• Series: Molecular Genetics & Genomic Medicine
• Subjects: electroretinography; lysosomal storage disease; retina; transmission electron microscopy; whole‐exome and genome sequencing
• Online Access: https://doi.org/10.1002/mgg3.1308

Abstract Background Biallelic CLN3 gene variants have been found in either juvenile‐onset neuronal ceroid lipofuscinosis (JNCL) or isolated retinal dystrophy. It has been reported that most JNCL patients carry a common 1.02‐kb deletion variant homozygously. Clinical characteristics of patients with biallelic CLN3 missense variants are not well elucidated. Methods We described a 26‐year‐old Japanese male patient with isolated retinal dystrophy. Whole‐exome sequencing (WES) and transmission electron microscopy (TEM) were performed. Results Whole‐exome sequencing identified a novel homozygous CLN3 missense variant [c.482C>T; p.(Ser161Leu)]. Ophthalmoscopy revealed retinal degeneration and macular atrophy, and later attenuated retinal vessels. Severely reduced responses were observed in both rod and cone electroretinograms. In TEM of the patient's lymphocytes, fingerprint profiles, which are specific findings in CLN3‐associated JNCL, were observed in 16/624 (2.56%) lymphocytes of the patient, who has never exhibited neurological signs during the 13‐year follow‐up period. Conclusion Our results indicated that this novel CLN3 missense variant is associated with teenage‐onset isolated retinal dystrophy. This is the first report of any patient with CLN3‐associated disorder in the Japanese population. Although fingerprint profiles have never been reported in CLN3‐associated isolated retinal dystrophy, these profiles were observed, albeit infrequently, suggesting that frequency of the fingerprint profiles might depend on variant types.