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CHRNB1 ‐associated congenital myasthenia syndrome: Expanding the clinical spectrum
Author(s) -
Freed Amanda S.,
Schwarz Anisha C.,
Brei Brianna K.,
Clowes Candadai Sarah V.,
Thies Jenny,
Mah Jean K.,
Chabra Shilpi,
Wang Leo,
Innes A. Micheil,
Bennett James T.
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62011
Subject(s) - exome sequencing , congenital myasthenic syndrome , genetic heterogeneity , myasthenia gravis , neuromuscular junction , exon , acetylcholine receptor , genetics , exome , biology , medicine , mutation , bioinformatics , gene , immunology , receptor , phenotype , neuroscience
CHRNB1 encodes the β subunit of the acetylcholine receptor (AChR) at the neuromuscular junction. Inherited defects in the neuromuscular junction can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous group of disorders which includes fetal akinesia deformation sequence (FADS) on the severe end of the spectrum. Here, we report two unrelated families with biallelic CHRNB1 variants, and in each family, one child presented with lethal FADS. We contrast the diagnostic odysseys in the two families, one of which lasted 16 years while the other, utilizing rapid exome sequencing, led to specific treatment in the first 2 weeks of life. Furthermore, we note that CHRNB1 variants may be under‐recognized because in both families, one of the variants is a single exon deletion that has been previously described but may not easily be detected in clinically available genetic testing.