CONGENITAL MYOPATHIES: NEMALINE AND TITINOPATHIES: P.232Core and rod myopathy due to a novel mutation in BTB domain of KBTBD13 gene presenting as LGMD

Abstract

A 59 years-old man complained about progressive pelvic and scapular girdles weakness since he was 50. Clinical examination revealed a generalized muscle hypertrophy, slowly movements and proximal muscle weakness. CK level ranged from 250 to 600 UI/L. Morphological data from three muscle biopsies were available. Nemaline rods were detected in two of three biopsies. ACTA1, RYR1, and NEB genes were initially ruled out. Because of muscle MRI features and clinical phenotype, mutation on POGLUT1 was suspected. Alpha-dystroglican showed normal immunostaining on muscle biopsy but reduction on WB. Molecular analysis of POGLUT1 was negative. Finally, a third biopsy was performed and revealed the presence of cores by optic microscopy whereas small rods were detected by electron microscopy. Type 2 hypotrophy was not observed in any of three muscle biopsies. Sanger sequencing revealed a novel missense mutation in BTB domain of KBTBD13 gene leading the diagnosis of core and rod myopathy. Mutation falls at the end of the alpha4 helix and seems to affect the self-association of BTB domain but not the BTB-Cul3 interaction. NGS panel for congenital myopathies ruled out other possible genes implicated in core and rod myopathies. Our findings expand clinical and genetical spectrum of core and rod myopathies.