Cargando…
Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome
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 o...
Autores principales: | , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9808558/ https://www.ncbi.nlm.nih.gov/pubmed/36379720 http://dx.doi.org/10.1101/mcs.a006242 |
_version_ | 1784862963383926784 |
---|---|
author | Reynolds, Hayley M. Wen, Ting Farrell, Andrew Mao, Rong Moore, Barry Boyden, Steven E. Bayrak-Toydemir, Pinar Nicholas, Thomas J. Rynearson, Shawn Holt, Carson Miller, Christine Noble, Katherine Bentley, Dawn Palmquist, Rachel Ostrander, Betsy Manberg, Stephanie Bonkowsky, Joshua L. Shayota, Brian J. Jenkins, Sabrina Malone |
author_facet | Reynolds, Hayley M. Wen, Ting Farrell, Andrew Mao, Rong Moore, Barry Boyden, Steven E. Bayrak-Toydemir, Pinar Nicholas, Thomas J. Rynearson, Shawn Holt, Carson Miller, Christine Noble, Katherine Bentley, Dawn Palmquist, Rachel Ostrander, Betsy Manberg, Stephanie Bonkowsky, Joshua L. Shayota, Brian J. Jenkins, Sabrina Malone |
author_sort | Reynolds, Hayley M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9808558 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98085582023-01-20 Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome Reynolds, Hayley M. Wen, Ting Farrell, Andrew Mao, Rong Moore, Barry Boyden, Steven E. Bayrak-Toydemir, Pinar Nicholas, Thomas J. Rynearson, Shawn Holt, Carson Miller, Christine Noble, Katherine Bentley, Dawn Palmquist, Rachel Ostrander, Betsy Manberg, Stephanie Bonkowsky, Joshua L. Shayota, Brian J. Jenkins, Sabrina Malone Cold Spring Harb Mol Case Stud Research Report 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. Cold Spring Harbor Laboratory Press 2022-12 /pmc/articles/PMC9808558/ /pubmed/36379720 http://dx.doi.org/10.1101/mcs.a006242 Text en © 2022 Reynolds et al.; Published by Cold Spring Harbor Laboratory Press https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited. |
spellingShingle | Research Report Reynolds, Hayley M. Wen, Ting Farrell, Andrew Mao, Rong Moore, Barry Boyden, Steven E. Bayrak-Toydemir, Pinar Nicholas, Thomas J. Rynearson, Shawn Holt, Carson Miller, Christine Noble, Katherine Bentley, Dawn Palmquist, Rachel Ostrander, Betsy Manberg, Stephanie Bonkowsky, Joshua L. Shayota, Brian J. Jenkins, Sabrina Malone Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome |
title | Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome |
title_full | Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome |
title_fullStr | Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome |
title_full_unstemmed | Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome |
title_short | Rapid genome sequencing identifies a novel de novo SNAP25 variant for neonatal congenital myasthenic syndrome |
title_sort | rapid genome sequencing identifies a novel de novo snap25 variant for neonatal congenital myasthenic syndrome |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9808558/ https://www.ncbi.nlm.nih.gov/pubmed/36379720 http://dx.doi.org/10.1101/mcs.a006242 |
work_keys_str_mv | AT reynoldshayleym rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT wenting rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT farrellandrew rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT maorong rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT moorebarry rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT boydenstevene rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT bayraktoydemirpinar rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT nicholasthomasj rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT rynearsonshawn rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT holtcarson rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT millerchristine rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT noblekatherine rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT bentleydawn rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT palmquistrachel rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT ostranderbetsy rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT manbergstephanie rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT bonkowskyjoshual rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT shayotabrianj rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome AT jenkinssabrinamalone rapidgenomesequencingidentifiesanoveldenovosnap25variantforneonatalcongenitalmyasthenicsyndrome |