TY - JOUR
T1 - CHRNB1-associated congenital myasthenia syndrome
T2 - Expanding the clinical spectrum
AU - Freed, Amanda S.
AU - Schwarz, Anisha C.
AU - Brei, Brianna K.
AU - Clowes Candadai, Sarah V.
AU - Thies, Jenny
AU - Mah, Jean K.
AU - Chabra, Shilpi
AU - Wang, Leo
AU - Innes, A. Micheil
AU - Bennett, James T.
N1 - Funding Information:
Arnold Lee Smith Endowed Professorship for Research Faculty Development; Burroughs Wellcome Fund, Grant/Award Number: 1014700; National Institute of General Medical Sciences, Grant/Award Number: 5T32GM007454; National Institutes of Health, Grant/Award Number: 2 R01 HL130996‐05 Funding information
Funding Information:
The authors would like to thank the families for allowing us to be involved in their care and share their stories so that we all may learn from them. Leo Wang would also like to thank Dr. Haley Anderson for her assistance with NCS. James T. Bennett and Amanda S. Freed would like to thank all of the members of the Rapid Inpatient Genomic Testing project team at Seattle Children's hospital who facilitated the rapid exome testing for family 1, as well as the Seattle Children's Focus on Kids Laboratory Guild for support. A. Micheil Innes and Jean K. Mah would like to thank Drs. Ross McLeod, Kym Boycott, Carsten Bonnemann as well as Linda MacLaren, Setareh Ashtiani, Carol Farr, and Sandra Donkevroot for their assistance in the previous or ongoing management and investigation of family 2. This work was supported by the Burroughs Welcome Fund Career Award for Medical Scientists (Grant No. 1014700 to James T. Bennett), the Arnold Lee Smith Endowed Professorship for Research Faculty Development, the National Institute of Health research project (Grant No. 2 R01 HL130996‐05 to James T. Bennett), and the postdoctoral training grant from the National Institute of General Medical Sciences of the National Institutes of Health (Grant No. 5T32GM007454 to Amanda S. Freed). Family #1 was presented as a poster at the David W. Smith Workshop on Malformations and Morphogenesis annual meeting in August 2018 and as an electronic poster at the American Academy of Neurology Meeting in May 2019.
Funding Information:
The authors would like to thank the families for allowing us to be involved in their care and share their stories so that we all may learn from them. Leo Wang would also like to thank Dr. Haley Anderson for her assistance with NCS. James T. Bennett and Amanda S. Freed would like to thank all of the members of the Rapid Inpatient Genomic Testing project team at Seattle Children's hospital who facilitated the rapid exome testing for family 1, as well as the Seattle Children's Focus on Kids Laboratory Guild for support. A. Micheil Innes and Jean K. Mah would like to thank Drs. Ross McLeod, Kym Boycott, Carsten Bonnemann as well as Linda MacLaren, Setareh Ashtiani, Carol Farr, and Sandra Donkevroot for their assistance in the previous or ongoing management and investigation of family 2. This work was supported by the Burroughs Welcome Fund Career Award for Medical Scientists (Grant No. 1014700 to James T. Bennett), the Arnold Lee Smith Endowed Professorship for Research Faculty Development, the National Institute of Health research project (Grant No. 2 R01 HL130996-05 to James T. Bennett), and the postdoctoral training grant from the National Institute of General Medical Sciences of the National Institutes of Health (Grant No. 5T32GM007454 to Amanda S. Freed). Family #1 was presented as a poster at the David W. Smith Workshop on Malformations and Morphogenesis annual meeting in August 2018 and as an electronic poster at the American Academy of Neurology Meeting in May 2019.
Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2021/3
Y1 - 2021/3
N2 - 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.
AB - 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.
KW - acetylcholinesterase inhibitor
KW - congenital myasthenia
KW - neuromuscular junction
KW - rapid exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85097279284&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097279284&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.62011
DO - 10.1002/ajmg.a.62011
M3 - Article
C2 - 33296147
AN - SCOPUS:85097279284
SN - 1552-4825
VL - 185
SP - 827
EP - 835
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 3
ER -