We have identified recessive RYR1 mutations in a patient with severe congenital NM, through high-throughput screening of congenital myopathy/muscular dystrophy-related genes using massively parallel sequencing with target gene capture.
We have examined the immunocytochemical expression of nebulin in skeletal muscle in 11 cases of nemaline myopathy, from ten families, with linkage compatible to chromosome 2q.22, the locus for nebulin.
We have examined endurance exercise as a means of improving recovery following muscle inactivity in our alpha-tropomyosin(slow)(Met9Arg)-transgenic mouse model of nemaline myopathy.
We evaluated the effects of mRK35 (a myostatin inhibitor developed by Pfizer) treatment in the TgACTA1D286G mouse model of NM. mRK35 induced skeletal muscle growth that led to significant increases in animal bodyweight, forelimb grip strength and muscle fiber force, although it should be noted that animal weight and forelimb grip strength in untreated TgACTA1D286G mice was not different from controls.
We establish a homozygous splice variant in TNNT3 as the likely cause of severe congenital NM with distal arthrogryposis, characterized by specific involvement of Type-2 fibers and deficiency of troponin-T<sub>fast</sub> .
We describe the presentation and six-year follow up of a child with nemaline myopathy due to a de novo mutation in the skeletal muscle α-actin gene (ACTA1) characterized by dramatic improvement during the early childhood years.
We describe muscle involvement using Whole-Body muscle Magnetic Resonance Imaging (WBMRI) in 8 individuals with genetically proven TPM2 mutations and different clinical and histological features (nemaline myopathy, 'cap disease', Bethlem-like phenotype, arthrogryposis).
We describe a novel, recessively inherited distal myopathy caused by homozygous missense mutations in the nebulin gene (NEB), in which other combinations of mutations are known to cause nemaline (rod) myopathy (NM).
We describe 3 young patients presenting congenital core-rod myopathy with bilateral foot-drop associated with autosomal recessive nebulin gene (NEB) mutations detected by exome sequencing.
We also report a sixth family in which a recurrent TPM3 mutation (p.Arg168His) was associated with histological features of CFTD and nemaline myopathy in different family members.
We also report a sixth family in which a recurrent TPM3 mutation (p.Arg168His) was associated with histological features of CFTD and nemaline myopathy in different family members.
Two other studies have reported single families that have features of both central core disease and nemaline myopathy (core/rod disease) caused by mutations in RYR1.
To provide further insights into the functional significance of the nebulin SH3 domain in the Z-disk and to understand the mechanisms by which truncations of nebulin lead to NM, we took two approaches: (1) an affinity-based proteomic screening to identify novel interaction partners of the nebulin SH3 domain; and (2) generation and characterization of a novel knockin mouse model with a premature stop codon in the nebulin gene, eliminating its C-terminal SH3 domain (NebΔSH3 mouse).
To date, we have studied 266 samples from 196 NM families using the NM-CGH microarray, and identified a novel recurrent NEB TRI variation in 13% (26/196) of the families and in 10% of the controls (6/60).
To date, only homozygous nonsense mutations or compound heterozygous truncating or internal deletion mutations in TNNT1 gene have been identified in NEM.
Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42.
Three genes are known to cause nemaline myopathy: the genes for nebulin (NEB) on chromosome 2q22, slow alpha-tropomyosin (TPM3) on chromosome 1q21 and skeletal muscle alpha-actin (ACTA1) on chromosome 1q42.