Fig. 1

Pedigree, clinical picture, and electron microscopy. In a family with an affected father, three affected and one unaffected sisters, the novel POLG variant c.3542G>A; p.Ser1181Asn co-segregates with the phenotype in two generations (a). Clinical features are distal atrophies and high-arched feet in the first (II.2) and second (II.3) oldest affected sister sitting on the right side and in the middle of the bench (b). The youngest sister (II.4) has a pronounced myopathic phenotype. An electron microscopy of the lateral vastus muscle obtained from patient II.2 revealed prominent intermyofibrillar autophagic vacuoles filled with pleomorphic granular and membranous material (c), degenerating mitochondria undergoing (abnormal) mitophagy (arrows; d, e), and paracrystalline inclusions in many mitochondria (arrows, f), demonstrating mitochondrial damage