Abstract
Congenital myasthenic syndrome (CMS) is a group of 32 disorders involving genetic dysfunction at the neuromuscular junction resulting in skeletal muscle weakness that worsens with physical activity. Precise diagnosis and molecular subtype identification are critical for treatment as medication for one subtype may exacerbate disease in another (Engel et al., Lancet Neurol 14: 420 [2015]; Finsterer, Orphanet J Rare Dis 14: 57 [2019]; Prior and Ghosh, J Child Neurol 36: 610 [2021]). The SNAP25-related CMS subtype (congenital myasthenic syndrome 18, CMS18; MIM #616330) is a rare disorder characterized by muscle fatigability, delayed psychomotor development, and ataxia. Herein, we performed rapid whole-genome sequencing (rWGS) on a critically ill newborn leading to the discovery of an unreported pathogenic de novo SNAP25 c.529C > T; p.Gln177Ter variant. In this report, we present a novel case of CMS18 with complex neonatal consequence. This discovery offers unique insight into the extent of phenotypic severity in CMS18, expands the reported SNAP25 variant phenotype, and paves a foundation for personalized management for CMS18.
| Original language | English |
|---|---|
| Article number | a006242 |
| Journal | Cold Spring Harbor Molecular Case Studies |
| Volume | 8 |
| Issue number | 7 |
| DOIs | |
| State | Published - Dec 2022 |
| Externally published | Yes |
Funding
The Utah NeoSeq Project is supported by the University of Utah Center for Genomic Medicine, ARUP Laboratories, the Ben B. and Iris M. Margolis Foundation, and the R. Harold Burton Foundation. Sequence alignment, variant calling, and variant interpretation analyses were performed at the Utah Center for Genetic Discovery Core facility, part of the Health Sciences Center Cores at the University of Utah. This work utilized resources and support from the Center for High Performance Computing at the University of Utah. The computational resources used were partially funded by the National Institutes of Health (NIH) Shared Instrumentation Grant 1S10OD021644-01A1. The Utah NeoSeq Project is supported by the University of Utah Center for Genomic Medicine, ARUP Laboratories, the Ben B. and Iris M. Margolis Foundation, and the R. Harold Burton Foundation. Sequence alignment, variant calling, and variant interpretation analyses were performed at the Utah Center for Genetic Discovery Core facility, part of the Health Sciences Center Cores at the University of Utah. This work utilized resources and support from the Center for High Performance Computing at the University of Utah. The computational resources used were partially funded by the National Institutes of Health (NIH) Shared Instrumentation Grant 1S10OD021644-01A1.