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Danon disease presenting with early onset of hypertrophic cardiomyopathy and peripheral pigmentary retinal dystrophy in a female with a de novo novel mosaic mutation in the LAMP2 gene

Meinert, Monika LU ; Englund, Elisabet LU ; Hedberg-Oldfors, Carola ; Oldfors, Anders ; Kornhall, Björn LU ; Lundin, Catarina LU and Wittström, Elisabeth LU (2019) In Ophthalmic Genetics 40(3). p.227-236
Abstract

Purpose: To describe the phenotype and genotype in a young woman with Danon disease. Methods: The patient underwent an ophthalmic examination including best corrected visual acuity (BCVA), fundus photography and fundus autofluorescence (FAF), full-field electroretinography (full-field ERG), multifocal ERG, optical coherence tomography (OCT) and SAP-Humphrey 30–2 at the ages of 20 and 25. Electrooculography, fluorescein angiography (FA), indocyanine angiography and OCT angiography were performed only once. Genetic testing using a Next-Generation Sequencing panel and immunohistochemical analysis of LAMP2 protein expression were performed in the patient’s explanted heart, and the patient’s cardiologic and ophthalmologic records were... (More)

Purpose: To describe the phenotype and genotype in a young woman with Danon disease. Methods: The patient underwent an ophthalmic examination including best corrected visual acuity (BCVA), fundus photography and fundus autofluorescence (FAF), full-field electroretinography (full-field ERG), multifocal ERG, optical coherence tomography (OCT) and SAP-Humphrey 30–2 at the ages of 20 and 25. Electrooculography, fluorescein angiography (FA), indocyanine angiography and OCT angiography were performed only once. Genetic testing using a Next-Generation Sequencing panel and immunohistochemical analysis of LAMP2 protein expression were performed in the patient’s explanted heart, and the patient’s cardiologic and ophthalmologic records were retrospectively reviewed. Results: A de novo, novel, mosaic mutation, c.135dupA; p.(Trp46Metfs*10) was identified in exon 2 of the LAMP2 gene. Immunohistochemical investigation of the myocardium in the explanted heart revealed pronounced deficiency of LAMP2 protein in cardiomyocytes. The color photographs, FAF images and FA revealed more extensive peripheral pigmentary retinal dystrophy (PPRD) at the 5-year follow-up examination. No changes were observed in BCVA, OCT, SAP-Humphrey 30–2 or multifocal ERG findings at follow-up. Full-field ERG showed an asymmetric interocular reduction in ERG response at follow-up: the b-wave amplitude of the rod response had decreased by 29% in the right eye, but by only 6 % in the left eye. The a-wave amplitude of single-flash response had decreased by 9 % in the left eye, while it had increased by 3% in the right eye. Conclusions: Although PPRD progressed slowly, it was an important clue in the diagnosis of the life-threatening condition of Danon disease.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Danon disease, hypertrophic cardiomyopathy, mosaic mutation in LAMP2, peripheral pigmentary retinal dystrophy
in
Ophthalmic Genetics
volume
40
issue
3
pages
11 pages
publisher
Taylor & Francis
external identifiers
  • scopus:85068603618
  • pmid:31264915
ISSN
1381-6810
DOI
10.1080/13816810.2019.1627464
project
Retinal structure, function and genetics in inherited and aquired retinal degenerative disease
language
English
LU publication?
yes
id
47d1c0f2-34c7-44c4-906e-591894f2b4b8
date added to LUP
2019-07-17 13:53:20
date last changed
2020-02-19 05:36:42
@article{47d1c0f2-34c7-44c4-906e-591894f2b4b8,
  abstract     = {<p>Purpose: To describe the phenotype and genotype in a young woman with Danon disease. Methods: The patient underwent an ophthalmic examination including best corrected visual acuity (BCVA), fundus photography and fundus autofluorescence (FAF), full-field electroretinography (full-field ERG), multifocal ERG, optical coherence tomography (OCT) and SAP-Humphrey 30–2 at the ages of 20 and 25. Electrooculography, fluorescein angiography (FA), indocyanine angiography and OCT angiography were performed only once. Genetic testing using a Next-Generation Sequencing panel and immunohistochemical analysis of LAMP2 protein expression were performed in the patient’s explanted heart, and the patient’s cardiologic and ophthalmologic records were retrospectively reviewed. Results: A de novo, novel, mosaic mutation, c.135dupA; p.(Trp46Metfs*10) was identified in exon 2 of the LAMP2 gene. Immunohistochemical investigation of the myocardium in the explanted heart revealed pronounced deficiency of LAMP2 protein in cardiomyocytes. The color photographs, FAF images and FA revealed more extensive peripheral pigmentary retinal dystrophy (PPRD) at the 5-year follow-up examination. No changes were observed in BCVA, OCT, SAP-Humphrey 30–2 or multifocal ERG findings at follow-up. Full-field ERG showed an asymmetric interocular reduction in ERG response at follow-up: the b-wave amplitude of the rod response had decreased by 29% in the right eye, but by only 6 % in the left eye. The a-wave amplitude of single-flash response had decreased by 9 % in the left eye, while it had increased by 3% in the right eye. Conclusions: Although PPRD progressed slowly, it was an important clue in the diagnosis of the life-threatening condition of Danon disease.</p>},
  author       = {Meinert, Monika and Englund, Elisabet and Hedberg-Oldfors, Carola and Oldfors, Anders and Kornhall, Björn and Lundin, Catarina and Wittström, Elisabeth},
  issn         = {1381-6810},
  language     = {eng},
  month        = {07},
  number       = {3},
  pages        = {227--236},
  publisher    = {Taylor & Francis},
  series       = {Ophthalmic Genetics},
  title        = {Danon disease presenting with early onset of hypertrophic cardiomyopathy and peripheral pigmentary retinal dystrophy in a female with a de novo novel mosaic mutation in the LAMP2 gene},
  url          = {http://dx.doi.org/10.1080/13816810.2019.1627464},
  doi          = {10.1080/13816810.2019.1627464},
  volume       = {40},
  year         = {2019},
}