Novel homozygous CLN3 missense variant in isolated retinal dystrophy: A case report and electron microscopic findings.
electroretinography
lysosomal storage disease
retina
transmission electron microscopy
whole-exome and genome sequencing
Journal
Molecular genetics & genomic medicine
ISSN: 2324-9269
Titre abrégé: Mol Genet Genomic Med
Pays: United States
ID NLM: 101603758
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
23
03
2020
revised:
27
04
2020
accepted:
28
04
2020
pubmed:
23
5
2020
medline:
12
5
2021
entrez:
23
5
2020
Statut:
ppublish
Résumé
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. We described a 26-year-old Japanese male patient with isolated retinal dystrophy. Whole-exome sequencing (WES) and transmission electron microscopy (TEM) were performed. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 32441891
doi: 10.1002/mgg3.1308
pmc: PMC7434607
doi:
Substances chimiques
CLN3 protein, human
0
Membrane Glycoproteins
0
Molecular Chaperones
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1308Informations de copyright
© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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