P.9.6 Combined cap disease and nemaline myopathy in the same patient caused by an autosomal dominant mutation in the TPM3 gene

Abstract

The slow alpha-tropomyosin gene (TPM3) has been associated with three distinct histological entities: nemaline myopathy (NM, NEM1), congenital fibres type disproportion (CFTD), and cap disease (CD). Here we describe a 34-year-old French Caucasian patient who presented global hypotonia from the age of three months. His examination at 19 years showed a long narrow face, bilateral ptosis, and high arched palate. He also presented diffuse axial weakness associated with some degree of upper limb girdle and distal lower limbs weakness. A right deltoid muscle biopsy effectuated at 19 years showed the presence of well separated cap structures and clusters of nemaline bodies. Electron microscopy (EM) confirmed the presence of characteristic cap structures and typical nemaline bodies. Exome sequencing analysis allowed us to identify a de novo missense mutation (p.Arg168Cys) in the TPM3 gene. With this report we describe a never reported association of combined cap disease and nemaline myopathy in a patient presenting a de novo mutation in the TPM3 gene. Our study enlarges the morphological spectrum TPM3-related myopathies, and proves that cap and nemaline bodies are two sides of the same ‘coin’. The slow alpha-tropomyosin gene (TPM3) has been associated with three distinct histological entities: nemaline myopathy (NM, NEM1), congenital fibres type disproportion (CFTD), and cap disease (CD). Here we describe a 34-year-old French Caucasian patient who presented global hypotonia from the age of three months. His examination at 19 years showed a long narrow face, bilateral ptosis, and high arched palate. He also presented diffuse axial weakness associated with some degree of upper limb girdle and distal lower limbs weakness. A right deltoid muscle biopsy effectuated at 19 years showed the presence of well separated cap structures and clusters of nemaline bodies. Electron microscopy (EM) confirmed the presence of characteristic cap structures and typical nemaline bodies. Exome sequencing analysis allowed us to identify a de novo missense mutation (p.Arg168Cys) in the TPM3 gene. With this report we describe a never reported association of combined cap disease and nemaline myopathy in a patient presenting a de novo mutation in the TPM3 gene. Our study enlarges the morphological spectrum TPM3-related myopathies, and proves that cap and nemaline bodies are two sides of the same ‘coin’.