Nemaline myopathy caused by tnnt1 mutations in a dutch pedigree

Abstract

Nemaline myopathy (NM) is genetically heterogeneous disorder characterized by early onset muscular weakness and sarcoplasmatic or intranuclear inclusions of rod-shaped Z-disk material in muscle fibers. Thus far, mutations in seven genes have been identified as cause of NM. Only one single TNNT1 nonsense mutation has been previously described that causes autosomal recessive NM in the old order Amish with a very specific clinical phenotype including rapidly progressive contractures. Here, we report a patient who is compound heterozygous for a c.309+1G>A mutation and an exon 14 deletion in the TNNT1 gene. This report confirms the specific clinical phenotype of TNNT1 NM and documents two new TNNT1 mutations outside the old order Amish.