Distal Involvement and Subsarcolemmal Minicore-Like Areas in a Case of POGLUT1-Associated Myopathy

Abstract

Pathogenic biallelic variants in POGLUT1 were linked to limb-girdle muscular dystrophy R21 (LGMD R21), a new type of LGMD featuring pelvic and shoulder girdle weakness, variable age of onset, slowly progressive course, and “inside-to-outside” fatty degeneration pattern in muscle magnetic resonance imaging (MRI). We describe a 54-year-old female with an infantile-onset, slowly progressive, pelvicgirdle myopathy, who later, after the age of 50, has developed finger flexors weakness. Muscle MRI revealed advanced fatty degeneration of the deeper thigh muscles, partially sparing the superficial regions (”inside-to-outside” pattern). Muscle biopsy showed pronounced myopathic features and internal structure disorganization, resembling minicore-like areas. Whole exome sequencing analysis identified a pathogenic homozygous variant in POGLUT1. By describing minicore-like areas and unique finger flexion involvement, in the absence of proximal upper limbs weakness, our case expands the histological and clinical spectrum of POGLUT1-associated myopathies. It further reinforces “inside-to-outside” muscle MRI pattern as a core diagnostic feature.