<scp><i>CHRNB1</i></scp>‐associated congenital myasthenia syndrome: Expanding the clinical spectrum

Freed, Amanda S.; Schwarz, Anisha; Brei, Brianna; Candadai, Sarah V. Clowes; Thies, Jenny; Mah, Jean K.; Chabra, Shilpi; Wang, Leo; Innes, A. Micheil; Bennett, James T.

doi:10.1002/ajmg.a.62011

Cited by 9 publications

(15 citation statements)

References 35 publications

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“…1,2,5 This three-pair deletion has been found in a patient who presented with congenital myasthenia syndrome and features of fetal akinesia deformation sequence, and it was reported as likely pathogenic. 5 The maternally inherited 2 kb pathogenic microdeletion at 17p13.1 includes the 3′ portion of the CHRNB1 gene and has been associated with exon 8 skipping or deletion leading to a frameshift and truncated protein. This microdeletion has been found in patients with severe autosomal recessive CMS.…”

Section: Discussionmentioning

confidence: 92%

“…Deletion of this exon is predicted to result in frameshifting and premature stop codon, likely leading to nonsense-mediated decay. 2,5 The paternally inherited three-base-pair deletion c.1218-9_1218-7, located nine base pairs upstream of the intron 9 splice acceptor site, was reported by the laboratory as a variant of unknown significance. However, this variant has been reported by Freed et al as "likely pathogenic" and is predicted to disrupt the splice acceptor site at the end of intron 9.…”

Section: Genetic Studiesmentioning

confidence: 99%

“…If this leads to inappropriate splicing of exon 9, it will likely lead to a premature truncating codon and nonsense-mediated decay similar to what has been described on the maternal exon 8 deletion. 5 A review of the literature identified a few reports describing CMS due to biallelic variants in CHRNB1. 2,[5][6][7]…”

Section: Genetic Studiesmentioning

confidence: 99%

“…5 A review of the literature identified a few reports describing CMS due to biallelic variants in CHRNB1. 2,[5][6][7]…”

Section: Genetic Studiesmentioning

confidence: 99%

“…Pathogenic variants in this gene are associated with both autosomal dominant and recessive forms, although only a few patients have been documented. 5 Here, we describe a patient with biallelic CHRNB1 variants and describe the clinical presentation, molecular findings, electrophysiologic results, and treatment response.…”

Section: Introductionmentioning

confidence: 99%

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Congenital myasthenic syndrome type 2C in a neonate: Redefining the phenotype of CHRNB1‐related myasthenic syndromes

Gonzalez,

Kayyal,

Zadeh

et al. 2023

Annals of the Child Neurology Society

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ObjectiveWe present a neonate with generalized weakness due to autosomal recessive congenital myasthenic syndrome type 2C (CMS2C) resulting from a compound heterozygous mutation in the CHRNB1 gene.Patient descriptionOur patient was determined by multiple methodologies to have a diagnosis of CMS2C (OMIM #616314). Whole‐genome sequencing revealed two distinct variants in the CHRNB1 gene (OMIM *100710): a maternally inherited 2 kb pathogenic microdeletion on chromosome 17p13.1 and a paternally inherited intronic deletion (c.1218‐9_1218‐7) that was reported by the laboratory as a variant of unknown significance.ConclusionsCMS2C is a rare autosomal recessive genetic condition associated with early‐onset muscle weakness. Our patient had a paternally inherited deletion in CHRNB1 (c.1218‐9_1218‐7) that was initially described as a variant of unknown significance. We suggest this finding is “likely pathogenic,” as this aberration has not been commonly described. He also had a partial deletion of CHRNB1 in the maternally inherited allele, which provides further evidence that partial gene deletions may be a more common molecular mechanism than previously known for this condition. The combination of the clinical presentation and electrophysiologic data allowed us to understand the molecular findings and ultimately diagnose CMS2C in our patient.

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Section: Discussionmentioning

confidence: 92%

Section: Genetic Studiesmentioning

confidence: 99%

Section: Genetic Studiesmentioning

confidence: 99%

“…5 A review of the literature identified a few reports describing CMS due to biallelic variants in CHRNB1. 2,[5][6][7]…”

Section: Genetic Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Congenital myasthenic syndrome type 2C in a neonate: Redefining the phenotype of CHRNB1‐related myasthenic syndromes

Gonzalez,

Kayyal,

Zadeh

et al. 2023

Annals of the Child Neurology Society

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Pyridostigmine

2021

Reactions Weekly

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Copious oral secretions: case reportIn a report of 2 patients, a boy [exact age at reaction not stated] was described, who exhibited copious oral secretions during treatment with pyridostigmine for congenital myasthenia syndrome (CMS).The boy, who was admitted due to CHRNB1-associated congenital CMS and fetal akinesia deformation sequence, started receiving oral pyridostigmine [dosage not stated] on the 17 th day of life. Subsequently, his condition improved. He developed a weak suck; however, there was no visible swallowing, and he was unable to take feeds by mouth. The treatment with pyridostigmine resulted in copious oral secretions [duration of treatment to reaction onset not stated], and his impaired swallowing function necessitated frequent suctioning. Thereafter, he was transitioned to comfort care. However, he died on 56 th day of life [exact cause of death not stated]. Autopsy was not performed.

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WGCNA and Machine Learning for Screening Potential Biomarkers in traumatic brain injury

Liu,

Zhao,

Zheng

2023

Preprint

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BackgroundTraumatic brain injury (TBI) is more common than ever and is becoming a global public health issue. However, there are no sensitive diagnostic or prognostic biomarkers to identify TBI, which leads to long-term consequences. In this study, we aim to identify genes that contribute to brain injury and to identify potential mechanisms for its progression in the early stages.MethodFrom the Gene Expression Omnibus (GEO) database, we downloaded GSE2871’s gene expression profiles. Weighted gene coexpression network analyses (WGCNA) were conducted on differentially expressed genes (DEGs), and the DEGs were analyzed by Gene Set Enrichment Analysis(GSEA). An enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed for understanding the biological functions of genes. The potential biomarkers were identified using 3 kinds of machine learning algorithms. Nomogram was constructed using the “rms” package. And the receiver operating characteristic curve (ROC) was plotted to detect and validate our prediction model sensitivity and specifificity.ResultsBetween samples with and without brain injury, 107 DEGs were identified, including 47 upregulated genes and 60 downregulated genes. On the basis of WGCNA and DEGs, 97 target genes were identified. In addition, biological function analysis indicated that target genes were primarily involved in the interaction of neuroactive ligands with receptors, taste transduction, cortisol synthesis and secretion, potassium ion transport. Based on machine learning algorithms, LOC103691092, Npw could be potentially useful biomarkers for TBI and showed good diagnostic values. Finally, a nomogram was constructed of the expression levels of these seven target genes to predict level of TBI, and the ROC showed that these genes can be used as hub genes after TBI.ConclusionLOC103691092, NPW, STK39, KCND3, APOC3, FOXE3, and CHRNB1 were identified as hub genes of TBI. These findings can provide a new direction for the diagnosis and treatment of TBI.

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CHRNB1‐associated congenital myasthenia syndrome: Expanding the clinical spectrum

Cited by 9 publications

References 35 publications

Congenital myasthenic syndrome type 2C in a neonate: Redefining the phenotype of CHRNB1‐related myasthenic syndromes

Congenital myasthenic syndrome type 2C in a neonate: Redefining the phenotype of CHRNB1‐related myasthenic syndromes

Pyridostigmine

WGCNA and Machine Learning for Screening Potential Biomarkers in traumatic brain injury

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