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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...

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Autores principales: Mizobuchi, Kei, Hayashi, Takaaki, Yoshitake, Kazutoshi, Fujinami, Kaoru, Tachibana, Toshiaki, Tsunoda, Kazushige, Iwata, Takeshi, Nakano, Tadashi
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
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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.
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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
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