Morphologic and Clinical Aspects of Danon Disease in a Patient with a Mutation c.137G &gt; A in the LAMP-2 Gene

Fidziańska, Anna; Madej-Pilarczyk, Agnieszka; Walczak, Ewa; Kuch, Marek

doi:10.1055/s-0033-1336017

Cited by 4 publications

(1 citation statement)

References 17 publications

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“…Two overlapping truncating mutations in the same region as (25,26). A de novo novel LAMP2 mutation, c.179delC, at the 3 end of exon 2, resulting in a frameshift with a premature stop codon, has been identified in a 14-year-old boy with Danon disease, exhibiting massive hypertrophic cardiomyopathy, mental retardation, and skeletal myopathy.…”

Section: Discussionmentioning

confidence: 99%

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

Englund

Hedberg‐Oldfors

et al. 2019

Ophthalmic Genetics

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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 lifethreatening condition of Danon disease.

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Section: Discussionmentioning

confidence: 99%

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

Englund

Hedberg‐Oldfors

et al. 2019

Ophthalmic Genetics

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Disappearance of left ventricular hypertrabeculation/noncompaction in vacuolar non-neuromuscular cardiomyopathy

Stöllberger¹,

Kolussi²,

Hackl³

et al. 2015

International Journal of Cardiology

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Review: Danon disease: Review of natural history and recent advances

Cenacchi

Papa

Pegoraro

et al. 2019

Neuropathology Appl Neurobio

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Danon disease is a severe multisystem disorder clinically characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation in male patients, and by a milder phenotype (predominantly involving cardiac muscle) in female patients. The disease is inherited as an X‐linked dominant trait. The primary deficiency of lysosome‐associated membrane protein‐2 (LAMP‐2) causes disruption of autophagy, leading to an impaired fusion of lysosomes to autophagosomes and biogenesis of lysosomes. We surveyed over 500 Danon disease patients reported in the literature from the first description to the present, in order to summarize the clinical, pathological and molecular data and treatment perspectives. An early molecular diagnosis is of crucial importance for genetic counselling and for therapeutic interventions: in male patients, the prognosis is poor due to rapid progression towards heart failure, and only heart transplantation modifies the disease course.

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Morphologic and Clinical Aspects of Danon Disease in a Patient with a Mutation c.137G > A in the LAMP-2 Gene

Abstract: Our immunohistochemical and ultrastructural findings reinforce the claim that in Danon disease the pathomechanism of chaperone-mediated autophagy in cardiomyocytes differs from that in skeletal muscle.

Cited by 4 publications

References 17 publications

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

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

Disappearance of left ventricular hypertrabeculation/noncompaction in vacuolar non-neuromuscular cardiomyopathy

Review: Danon disease: Review of natural history and recent advances

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