Proteomic and morphological insights and clinical presentation of two young patients with novel mutations of BVES (POPDC1).

Popeye domain containing protein 1 (POPDC1) is a highly conserved transmembrane protein essential for striated muscle function and homeostasis. Pathogenic variants in the gene encoding POPDC1 (BVES, Blood vessel epicardial substance) are causative for limb-girdle muscular dystrophy (LGMDR25), associated with cardiac arrhythmia. We report on four affected children (age 7-19 years) from two consanguineous families with two novel pathogenic variants in BVES c.

Heterozygous POLG variant Ser1181Asn co-segregating in a family with autosomal dominant axonal neuropathy, proximal muscle fatigability, ptosis, and ragged red fibers.

By whole-exome sequencing, we found the heterozygous POLG variant c.3542G>A; p.Ser1181Asn in a family of four affected individuals, presenting with a mixed neuro-myopathic phenotype.

The p.Ala2430Val mutation in filamin C causes a "hypertrophic myofibrillar cardiomyopathy".

Hypertrophic cardiomyopathy (HCM) often leads to heart failure. Mutations in sarcomeric proteins are most frequently the cause of HCM but in many patients the gene defect is not known. Here we report on a young man who was diagnosed with HCM shortly after birth.