CHRNB1-associated congenital myasthenia syndrome: Expanding the clinical spectrum.
acetylcholinesterase inhibitor
congenital myasthenia
neuromuscular junction
rapid exome sequencing
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
26
06
2020
revised:
28
10
2020
accepted:
30
10
2020
pubmed:
10
12
2020
medline:
3
8
2021
entrez:
9
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33296147
doi: 10.1002/ajmg.a.62011
doi:
Substances chimiques
CHRNB1 protein, human
0
Receptors, Nicotinic
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
827-835Subventions
Organisme : NIGMS NIH HHS
ID : 5T32GM007454
Pays : United States
Organisme : NIH HHS
ID : 2 R01 HL130996-05
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals LLC.
Références
Abicht, A., Müller, J. S., & Lochmüller, H. (2016). Congenital myasthenic syndromes. In M. P. Adam, H. H. Ardinger, & R. A. Pagon (Eds.), GeneReviews®. Seattle (WA): University of Washington, Seattle.
Adzhubei, I. A., Schmidt, S., Peshkin, L., Ramensky, V. E., Gerasimova, A., Bork, P., … Sunyaev, S. R. (2010). A method and server for predicting damaging missense mutations. Nature Methods, 7(4), 248-249. https://doi.org/10.1038/nmeth0410-248
Brnich, S. E., Abou Tayoun, A. N., Couch, F. J., Cutting, G. R., Greenblatt, M. S., Heinen, C. D., … Clinical Genome Resource Sequence Variant Interpretation Working Group. (2019). Recommendations for application of the functional evidence PS3/BS3 criterion using the ACMG/AMP sequence variant interpretation framework. Genome Medicine, 12(1), 3. https://doi.org/10.1186/s13073-019-0690-2
Chen, C. P. (2012). Prenatal diagnosis and genetic analysis of fetal akinesia deformation sequence and multiple pterygium syndrome associated with neuromuscular junction disorders: A review. Taiwan Journal of Obstetrics and Gynecology, 51(1), 12-17. https://doi.org/10.1016/j.tjog.2012.01.004
Desmet, F. O., Hamroun, D., Lalande, M., Collod-Beroud, G., Claustres, M., & Beroud, C. (2009). Human splicing finder: An online bioinformatics tool to predict splicing signals. Nucleic Acids Research, 37(9), e67. https://doi.org/10.1093/nar/gkp215
Engel, A. G. (2018). Genetic basis and phenotypic features of congenital myasthenic syndromes. Handbook of Clinical Neurology, 148, 565-589. https://doi.org/10.1016/B978-0-444-64076-5.00037-5
Engel, A. G., Shen, X. M., Selcen, D., & Sine, S. M. (2015). Congenital myasthenic syndromes: Pathogenesis, diagnosis, and treatment. Lancet Neurology, 14(4), 420-434. https://doi.org/10.1016/S1474-4422(14)70201-7
Filges, I., & Hall, J. G. (2013). Failure to identify antenatal multiple congenital contractures and fetal akinesia-Proposal of guidelines to improve diagnosis. Prenatal Diagnosis, 33(1), 61-74. https://doi.org/10.1002/pd.4011
Freed, A. S., Clowes Candadai, S. V., Sikes, M. C., Thies, J., Byers, H. M., Dines, J. N., … Bennett, J. T. (2020). The impact of rapid exome sequencing on medical management of critically ill children. Journal of Pediatrics, S0022-3476(20), 30721-30726. https://doi.org/10.1016/j.jpeds.2020.06.020
Hall, J. G. (2009). Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited. Birth Defects Researc Part A: Clinical and Molecular Teratology, 85(8), 677-694. https://doi.org/10.1002/bdra.20611
Karczewski, K. J., Francioli, L. C., Tiao, G., Cummings, B. B., Alföldi, J., Wang, Q., … MacArthur, D. G. (2020). The mutational constraint spectrum quantified from variation in 141,456 humans. Nature, 581(7809), 434-443. https://doi.org/10.1038/s41586-020-2308-7
Kingsmore, S. F. (2016). Newborn testing and screening by whole-genome sequencing. Genetics in Medicine, 18(3), 214-216. https://doi.org/10.1038/gim.2015.172
Lek, M., Karczewski, K. J., Minikel, E. V., Samocha, K. E., Banks, E., Fennell, T., … Exome Aggregation Consortium. (2016). Analysis of protein-coding genetic variation in 60,706 humans. Nature, 536(7616), 285-291. https://doi.org/10.1038/nature19057
Michalk, A., Stricker, S., Becker, J., Rupps, R., Pantzar, T., Miertus, J., … Hoffmann, K. (2008). Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders. American Journal of Human Genetics, 82(2), 464-476. https://doi.org/10.1016/j.ajhg.2007.11.006
Pergande, M., Motameny, S., Özdemir, Ö., Kreutzer, M., Wang, H., Daimagüler, H. S., … Cirak, S. (2020). The genomic and clinical landscape of fetal akinesia. Genetics in Medicine, 22(3), 511-523. https://doi.org/10.1038/s41436-019-0680-1
Quiram, P. A., Ohno, K., Milone, M., Patterson, M. C., Pruitt, N. J., Brengman, J. M., … Engel, A. G. (1999). Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly. Journal of Clinical Investigations, 104(10), 1403-1410. https://doi.org/10.1172/JCI8179
Ravenscroft, G., Sollis, E., Charles, A. K., North, K. N., Baynam, G., & Laing, N. G. (2011). Fetal akinesia: Review of the genetics of the neuromuscular causes. Journal of Medical Genetics, 48(12), 793-801. https://doi.org/10.1136/jmedgenet-2011-100211
Retterer, K., Juusola, J., Cho, M., Vitazka, P., Millan, F., Gibelline, F., … Bale, S. (2016). Clinical application of whole-exome sequencing across clinical indications. Genetics in Medicine, 18(7), 696-704. https://doi.org/10.1038/gim.2015.148
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., … Committee, A. L. Q. A. (2015). Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 17(5), 405-424. https://doi.org/10.1038/gim.2015.30
Schouten, J. P., McElgunn, C. J., Waaijer, R., Zwijnenburg, D., Diepvens, F., & Pals, G. (2002). Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Ressearch, 30(12), e57.
Schwarz, J. M., Cooper, D. N., Schuelke, M., & Seelow, D. (2014). MutationTaster2: Mutation prediction for the deep-sequencing age. Nature Methods, 11(4), 361-362. https://doi.org/10.1038/nmeth.2890
Shen, X. M., Di, L., Shen, S., Zhao, Y., Neumeye, A. M., Selcen, D., … Engel, A. G. (2020). A novel fast channel myasthenia caused by mutation in β subunit of AChR reveals sub-unit specific contribution of the intracellular M1-M2 linker to channel gating. Experimental Neurology, 331, 113375. https://doi.org/10.1016/j.expneurol.2020.113375
Shen, X. M., Okuno, T., Milone, M., Otsuka, K., Takahashi, K., Komaki, H., … Engel, A. G. (2016). Mutations causing slow-channel myasthenia reveal that a valine ring in the channel pore of muscle AChR is optimized for stabilizing channel gating. Human Mutation, 37(10), 1051-1059. https://doi.org/10.1002/humu.23043
Sim, N. L., Kumar, P., Hu, J., Henikoff, S., Schneider, G., & Ng, P. C. (2012). SIFT web server: Predicting effects of amino acid substitutions on proteins. Nucleic Acids Research, 40, W452-W457. https://doi.org/10.1093/nar/gks539
Stark, Z., Tan, T. Y., Chong, B., Brett, G. R., Yap, P., Walsh, M., … White, S. M. (2016). A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders. Genetics in Medicine, 18(11), 1090-1096. https://doi.org/10.1038/gim.2016.1
Tartaglia, N. R., Howell, S., Sutherland, A., Wilson, R., & Wildon, L. (2010). A review of trisomy X (47,XXX). Orphanet Journal of Rare Diseases, 5, 8. https://doi.org/10.1186/1750-1172-5-8
The UniProt Consortium. (2019). UniProt: A worldwide hub of protein knowledge. Nucleic Acids Research, 47(D1), D506-D515. https://doi.org/10.1093/nar/gky1049
Todd, E. J., Yau, K. S., Ong, R., Slee, J., McGillivray, G., Barnett, C. P., … Ravenscroft, G. (2015). Next generation sequencing in a large cohort of patients presenting with neuromuscular disease before or at birth. Orphanet Journal of Rare Diseases, 10, 148. https://doi.org/10.1186/s13023-015-0364-0
Vogt, J., Harrison, B. J., Spearman, H., Cossins, J., Vermeet, S., ten Cate, L. N., … Maher, E. R. (2008). Mutation analysis of CHRNA1, CHRNB1, CHRND and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients. American Journal of Human Genetics, 82(1), 222-227. https://doi.org/10.1016/j.ajhg.2007.09.016
Wilbe, M., Ekvall, S., Eurenius, K., Ericson, K., Casar-Borota, O., Klar, J., … Bondeson, M. L. (2015). MuSK: A new target for lethal fetal akinesia deformation sequence (FADS). Journal of Medical Genetics, 52(3), 195-202. https://doi.org/10.1136/jmedgenet-2014-102730
Willig, L. K., Petrikin, J. E., Smith, L. D., Saunders, C. J., Thiffault, I., Miller, N. A., … Kingsmore, S. F. (2015). Whole-genome sequencing for identification of Mendelian disorders in critically ill infants: A retrospective analysis of diagnostic and clinical findings. Lancet Respiraatory Medicine, 3(5), 377-387. https://doi.org/10.1016/S2213-2600(15)00139-3
Yeo, G., & Burge, C. B. (2004). Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. Journal of Computational Biology, 11(2-3), 377-394. https://doi.org/10.1089/1066527041410418