Two Japanese LGMDR25 patients with a biallelic recurrent nonsense variant of BVES
Introduction
POPDC1, the protein product of the BVES gene, is predominantly expressed in striated muscles, highest in skeletal muscles [1]. BVES variants are associated with limb-girdle muscular dystrophy autosomal recessive 25 (LGMDR25), characterized by slowly progressive muscular dystrophy and stress-induced atrioventricular (AV) block [2,3]. Mutant zebrafish in which BVES has been knocked down display muscle fiber disorganization. They also have lower cyclic adenosine 3’,5’-monophosphate binding ability than wildtype counterparts, resulting in TREK-1 current modulation disturbance [2]. Moreover, POPDC1 is also known as caveolae-associated protein; the cardiomyocytes of BVES-null mutant mice exhibit impaired calcium ion profiles, decreased ischemia tolerance, and fewer caveolae than wildtype cardiomyocytes [4]. To date, seven LGMDR25 patients from four unrelated families from Albanian, North Africa, and Belgium have been reported; each family had a different variant: a missense, start-loss, stop-gain, or splicing site variant [2,3]. Here, we present two Japanese patients with a novel recurrent homozygous nonsense BVES variant.
Section snippets
Case reports
Patient 1 is a 67-year-old Japanese man, born to consanguineous parents, with a history of exercise-induced myalgia in the thigh and calf muscles since childhood. His neck and wrist flexion ranges of motion had also been mildly limited since childhood. At 40 years of age, he presented with AV block and dilated cardiomyopathy, and had a pacemaker implanted. At 45 years of age, he displayed gait disturbance and lordosis. Upper limbs weakness was noticed at 57 years of age. Although his symptoms
Discussion
We identified two patients with LGMDR25 (alternatively called LGMD2X). LGMDR25 is characterized by slowly progressive adult-onset muscular dystrophy accompanied by the cardiac conduction abnormality AV block. Seven cases from four unrelated families with variable skeletal muscle phenotypes have been described; four of the seven patients had skeletal muscle involvement and only two of the seven experienced apparent muscle weakness [2,3]. In this section, we focus on the skeletal muscle
Acknowledgements
We thank Megumu Ogawa and Hisayoshi Nakamura for their help. We also thank the patients and their family members for making this work possible.
Funding
This study was supported partly by Intramural Research Grants for Neurological and Psychiatric Disorders of NCNP [grant numbers 2-5, 2-6, 29-4 and 30-9]; AMED [grant numbers JP20ek0109490h0001 and JP20ek0109348s0503]; and Joint Usage and Joint Research Programs, the Institute of Advanced Medical Sciences, Tokushima University [2019, A9 to AI]. The funding sources had no role in the study design, data collection, data analysis, report writing, and submission decision.
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Proteomic and morphological insights and clinical presentation of two young patients with novel mutations of BVES (POPDC1)
2022, Molecular Genetics and MetabolismCitation Excerpt :Two of them had an AV block [6]. Indrawati and colleagues described two Japanese patients with the pathogenic BVES variant c.788C>A, p.S263X and onset of muscle weakness at age 44 and 45 years, respectively [8]. Recently, Beecher and colleagues reported a juvenile patient from India with a c.427A>T, p.R143X variant in BVES presenting with muscle weaknes [7].
Phosphodiesterase type 4 anchoring regulates cAMP signaling to Popeye domain-containing proteins
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Severe adolescent-onset limb-girdle muscular dystrophy due to a novel homozygous nonsense BVES variant
2021, Journal of the Neurological Sciences