Two Japanese LGMDR25 patients with a biallelic recurrent nonsense variant of BVES

Severe adolescent-onset limb-girdle muscular dystrophy due to a novel homozygous nonsense BVES variant

“…POPDC1 is also expressed in caveolae and reduced numbers of caveolae have been reported in Popdc1 null mutant mice and an LGMDR25 patient [3]. To date, only 9 LGMDR25 patients have been described (Table 1) [1,3,4]. Herein, we report a patient with adolescent-onset lower limb weakness due to a novel homozygous nonsense BVES variant.…”

“…Four had myalgia or syncope without weakness, 2 of whom were in their fifth decade. [1,3,4]. Distribution of weakness appears highly variable, however, the majority demonstrate proximal lower limb involvement and periscapular weakness was present in 3.…”

“…POPDC1 binds cyclic 3 ′ ,5 ′ -adenosine monophosphate (cAMP) and loss of popdc1 expression in zebrafish leads to development of atrioventricular (AV) block and abnormal skeletal muscle development [1]. POPDC1 is also expressed in caveolae and reduced numbers of caveolae have been reported in Popdc1 null mutant mice and an LGMDR25 patient [3]. To date, only 9 LGMDR25 patients have been described (Table 1) [1,3,4].…”

Phosphodiesterase Type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins

“…POPDC1 is expressed most abundantly in striated muscle, i.e. heart and skeletal muscle, and these tissues are affected in patients harboring POPDC1 mutations (De Ridder et al, 2019;Indrawati et al, 2020;Schindler et al, 2016). However, POPDC1 is also found in smooth muscle cells, the gastrointestinal tract, uterus and bladder, neurons of the central and autonomous nervous system and epithelial cells (Andree et al, 2000;Smith & Bader, 2006;Vasavada et al, 2004).…”

“…Loss-of-function mutations of Popdc1 and Popdc2 in mice and zebrafish established an important role for these genes in cardiac pacemaking and conduction ((Froese et al, 2012;Kirchmaier et al, 2012;Schindler et al, 2016). Mutations in POPDC1, POPDC2 and POPDC3 have been recently identified in patients suffering from cardiac arrhythmia and/or limb-girdle muscular dystrophy, respectively ((De Ridder et al, 2019;Indrawati et al, 2020;Schindler et al, 2016;Vissing et al, 2019). Moreover, POPDC proteins have also been implicated in atrial fibrillation, long QT syndrome and heart failure (Gingold-Belfer et al, 2011;Tan et al, 2013;Wang et al, 2016).…”