Usher syndrome and Nebulin-associated myopathy in a single patient due to variants in MYO7A and NEB.
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ABSTRACT:
SUBMITTER: Maia N
PROVIDER: S-EPMC7752365 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Usher syndrome and Nebulin-associated myopathy in a single patient due to variants in <i>MYO7A</i> and <i>NEB</i>.
Maia Nuno N Soares Ana Rita AR Fortuna Ana Maria AM Marques Isabel I Gonçalves Ana A Santos Rosário R Melo Pires Manuel M de Brouwer Arjan P M APM Jorge Paula P
Clinical case reports 20200730 12
In a patient with Usher syndrome and atypical muscle complaints, we have identified two separate variants in <i>MYO7A</i> and<i>NEB</i> genes by exome sequencing. The homozygous variants in these two recessive genes could explain the full phenotype of our patient. ...[more]
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Project description:Recessive nebulin (NEB) mutations are a common cause of nemaline myopathy (NM), typically characterized by generalized weakness of early-onset and nemaline rods on muscle biopsy. Exceptional adult cases with additional cores and an isolated distal weakness have been reported. The large NEB gene with 183 exons has been an obstacle for the genetic work-up. Here we report a childhood-onset case with distal weakness and a core-rod myopathy, associated with recessive NEB mutations identified by next generation sequencing (NGS). This 6-year-old boy presented with a history of gross-motor difficulties following a normal early development. He had distal leg weakness with bilateral foot drop, as well as axial muscle weakness, scoliosis and spinal rigidity; additionally he required nocturnal respiratory support. Muscle magnetic resonance (MR) imaging showed distal involvement in the medial and anterior compartment of the lower leg. A muscle biopsy featured both rods and cores. Initial targeted testing identified a heterozygous Nebulin exon 55 deletion. Further analysis using NGS revealed a frameshifting 4 bp duplication, c.24372_24375dup (P.Val8126fs), on the opposite allele. This case illustrates that NEB mutations can cause childhood onset distal NM, with additional cores on muscle biopsy and proves the diagnostic utility of NGS for myopathies, particularly when large genes are implicated.
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