Two novel nebulin variants in an adult patient with congenital nemaline myopathy.
Congenital myopathies are clinically and genetically heterogeneous disorders, which often remain genetically undiagnosed for many years. Here we present a 40-year old patient with an almost lifelong history of a congenital myopathy of unknown cause. Muscle biopsy in childhood revealed mild myopathic features and rods. Clinical examination on presentation at the age of 40 revealed a facial weakness, atrophy and weakness of the arm muscles and distal leg muscles with mild contractures of the foot flexors and the right elbow. Subsequently, the nebulin gene was identified as a putative candidate gene by linkage analyses, but sequence analysis only revealed one heterozygous splice site mutation in intron 73 (c.10872+1G>T). Therefore, "Next Generation Sequencing" was performed, which revealed a second pathogenic variant in exon 145 (c.21622A>C). Compound-heterozygous carrier status was confirmed via sequence analysis of the index patient's parents. Whole body muscle MRI showed a muscle involvement as previously described in nebulin-associated myopathies. Based on biopsy material, genetic analyses and muscle MRI, we identified two novel, compound-heterozygous variants in the nebulin gene after a 30 year clinical history, which cause a classical childhood type of nemaline myopathy.
Neurologische Klinik, Heimer-Institut am Bergmannsheil, Ruhr-Universität Bochum, Bochum, Germany. Electronic address: anne.guettsches@rub.de.
Anne K
AK
Güttsches
Abteilung für Humangenetik, Ruhr-Universität Bochum, Bochum, Germany.
Gabriele
G
Dekomien
Neurologische Klinik, RWTH Aachen University, Aachen, Germany; Institut für Neuropathologie, RWTH Aachen University, Aachen, Germany.
Kristl G
KG
Claeys
Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
Maja
M
von der Hagen
Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
Angela
A
Huebner
Neurologische Klinik, Heimer-Institut am Bergmannsheil, Ruhr-Universität Bochum, Bochum, Germany.
Rudolf A
RA
Kley
Klinik für Neuropädiatrie und Muskelerkrankungen, Universitätskinderklinik Freiburg, Freiburg, Germany.
Janbernd
J
Kirschner
Neurologische Klinik, Heimer-Institut am Bergmannsheil, Ruhr-Universität Bochum, Bochum, Germany.
Matthias
M
Vorgerd
D000328:Adult; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009124:Muscle Proteins / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D017696:Myopathies, Nemaline / Q000235:genetics*
D009124:Muscle Proteins; C035620:nebulin
Congenital myopathy; Nebulin (NEB) associated myopathies; Nemaline rods; Next Generation Sequencing; Whole body muscle MRI