Cargando…
Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings
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 bialleli...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434607/ https://www.ncbi.nlm.nih.gov/pubmed/32441891 http://dx.doi.org/10.1002/mgg3.1308 |
_version_ | 1783572184498700288 |
---|---|
author | Mizobuchi, Kei Hayashi, Takaaki Yoshitake, Kazutoshi Fujinami, Kaoru Tachibana, Toshiaki Tsunoda, Kazushige Iwata, Takeshi Nakano, Tadashi |
author_facet | Mizobuchi, Kei Hayashi, Takaaki Yoshitake, Kazutoshi Fujinami, Kaoru Tachibana, Toshiaki Tsunoda, Kazushige Iwata, Takeshi Nakano, Tadashi |
author_sort | Mizobuchi, Kei |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7434607 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74346072020-08-20 Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings Mizobuchi, Kei Hayashi, Takaaki Yoshitake, Kazutoshi Fujinami, Kaoru Tachibana, Toshiaki Tsunoda, Kazushige Iwata, Takeshi Nakano, Tadashi Mol Genet Genomic Med Clinical Reports 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. John Wiley and Sons Inc. 2020-05-22 /pmc/articles/PMC7434607/ /pubmed/32441891 http://dx.doi.org/10.1002/mgg3.1308 Text en © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Clinical Reports Mizobuchi, Kei Hayashi, Takaaki Yoshitake, Kazutoshi Fujinami, Kaoru Tachibana, Toshiaki Tsunoda, Kazushige Iwata, Takeshi Nakano, Tadashi Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings |
title | Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings |
title_full | Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings |
title_fullStr | Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings |
title_full_unstemmed | Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings |
title_short | Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings |
title_sort | novel homozygous cln3 missense variant in isolated retinal dystrophy: a case report and electron microscopic findings |
topic | Clinical Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434607/ https://www.ncbi.nlm.nih.gov/pubmed/32441891 http://dx.doi.org/10.1002/mgg3.1308 |
work_keys_str_mv | AT mizobuchikei novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings AT hayashitakaaki novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings AT yoshitakekazutoshi novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings AT fujinamikaoru novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings AT tachibanatoshiaki novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings AT tsunodakazushige novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings AT iwatatakeshi novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings AT nakanotadashi novelhomozygouscln3missensevariantinisolatedretinaldystrophyacasereportandelectronmicroscopicfindings |