|Title||Biallelic Pathogenic Variants in Associated With Congenital Myopathy.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Calame, DG, Fatih, J, Herman, I, Akdemir, ZCoban, Du, H, Jhangiani, SN, Gibbs, RA, Marafi, D, Pehlivan, D, Posey, JE, Lotze, T, Mancias, P, Bhattacharjee, MBidwai, Lupski, JR|
|Date Published||2021 Jun|
OBJECTIVE: Pathogenic variants in , the gene encoding fast skeletal muscle troponin T, were first described in autosomal dominant distal arthrogryposis type 2B2. Recently, a homozygous splice site variant, c.681+1G>A, was identified in a patient with nemaline myopathy and distal arthrogryposis. Here, we describe the second individual with congenital myopathy associated with biallelic variants.
METHODS: Clinical exome sequencing data from a patient with molecularly undiagnosed congenital myopathy underwent research reanalysis. Clinical and histopathologic data were collected and compared with the single reported patient with -related congenital myopathy.
RESULTS: A homozygous variant, c.481-1G>A, was identified. This variant alters a consensus splice acceptor and is predicted to affect splicing by multiple prediction tools. Both the patient reported here and the previously published patient exhibited limb, bulbar, and respiratory muscle weakness from birth, which improved over time. Other shared features include history of polyhydramnios, hypotonia, scoliosis, and high-arched palate. Distal arthrogryposis and nemaline rods, findings reported in the first patient with -related congenital myopathy, were not observed in the patient reported here.
CONCLUSIONS: This report provides further evidence for the association of biallelic variants with severe recessive congenital myopathy with or without nemaline rods and distal arthrogryposis. sequencing and copy number analysis should be incorporated into the workup of congenital myopathies.
|Alternate Journal||Neurol Genet|
|PubMed Central ID||PMC8105884|
|Grant List||R35 NS105078 / NS / NINDS NIH HHS / United States |
UM1 HG006542 / HG / NHGRI NIH HHS / United States