Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25557463
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Autophagic vacuolar pathology in desminopathies
#MMPMID25557463
Weihl CC
; Iyadurai S
; Baloh RH
; Pittman SK
; Schmidt RE
; Lopate G
; Pestronk A
; Harms MB
Neuromuscul Disord
2015[Mar]; 25
(3
): 199-206
PMID25557463
show ga
Autophagic vacuolar myopathies are an emerging group of muscle diseases with
common pathologic features. These include autophagic vacuoles containing both
lysosomal and autophagosomal proteins sometimes lined with sarcolemmal proteins
such as dystrophin. These features have been most clearly described in patients
with Danon's disease due to LAMP2 deficiency and X-linked myopathy with excessive
autophagy (XMEA) due to mutations in VMA21. Disruptions of these proteins lead to
lysosomal dysfunction and subsequent autophagic vacuolar pathology. We performed
whole exome sequencing on two families with autosomal dominantly inherited
myopathies with autophagic vacuolar pathology and surprisingly identified a
p.R454W tail domain mutation and a novel p.S6W head domain mutation in desmin,
DES. In addition, re-evaluation of muscle tissue from another family with a novel
p.I402N missense DES mutation also identified autophagic vacuoles. We suggest
that autophagic vacuoles may be an underappreciated pathology present in
desminopathy patient muscle. Moreover, autophagic vacuolar pathology can be due
to genetic etiologies unrelated to primary defects in the lysosomes or autophagic
machinery. Specifically, cytoskeletal derangement and the accumulation of
aggregated proteins such as desmin may activate the autophagic system leading to
the pathologic features of an autophagic vacuolar myopathy.
free
free
free
