The longest reported sibling survivors of a severe form of congenital myasthenic syndrome with the ALG14 pathogenic variant.
ALG14
congenital disorders of glycosylation
congenital myasthenic syndrome
repetitive nerve stimulation test
whole-exome sequence
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:
04 2022
04 2022
Historique:
revised:
26
10
2021
received:
23
07
2021
accepted:
07
12
2021
pubmed:
1
1
2022
medline:
19
4
2022
entrez:
31
12
2021
Statut:
ppublish
Résumé
Congenital myasthenic syndromes (CMS) is a group of diseases that causes abnormalities at the neuromuscular junction owing to genetic anomalies. The pathogenic variant in ALG14 results in a severe pathological form of CMS causing end-plate acetylcholine receptor deficiency. Here, we report the cases of two siblings with CMS associated with a novel variant in ALG14. Immediately after birth, they showed hypotonia and multiple joint contractures with low Apgar scores. Ptosis, low-set ears, and high-arched palate were noted. Deep tendon reflexes were symmetrical. They showed worsening swallowing and respiratory problems; hence, nasal feeding and tracheotomy were performed. Cranial magnetic resonance imaging scans revealed delayed myelination and cerebral atrophy. Exome sequencing indicated that the siblings had novel compound heterozygous missense variants, c.590T>G (p.Val197Gly) and c.433G>A (p.Gly145Arg), in exon 4 of ALG14. Repetitive nerve stimulation test showed an abnormal decrease in compound muscle action potential. After treatment with pyridostigmine, the time off the respirator increased. Their epileptic seizures were well controlled by anti-epileptic drugs. Their clinical course is stable even now at the ages of 5 and 2 years, making them the longest reported survivors of a severe form of CMS with the ALG14 variant thus far.
Identifiants
pubmed: 34971077
doi: 10.1002/ajmg.a.62629
doi:
Types de publication
Case Reports
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1293-1298Informations de copyright
© 2021 Wiley Periodicals LLC.
Références
Chan, Y. M., Keramaris-Vrantsis, E., Lidov, H. G., Norton, J. H., Zinchenko, N., Gruber, H. E., Thresher, R., Blake, D. J., Ashar, J., Rosenfeld, J., & Lu, Q. L. (2010). Fukutin-related protein is essential for mouse muscle, brain and eye development and mutation recapitulates the wide clinical spectrums of dystroglycanopathies. Human Molecular Genetics, 19(20), 3995-4006. https://doi.org/10.1093/hmg/ddq314
Cossins, J., Belaya, K., Hicks, D., Salih, M. A., Finlayson, S., Carboni, N., Liu, W. W., Maxwell, S., Zoltowska, K., Farsani, G. T., Laval, S., Seidhamed, M. Z., WGS500 Consortium, Donnelly, P., Bentley, D., McGowan, S. J., Müller, J., Palace, J., Lochmüller, H., & Beeson, D. (2013). Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain, 136(Pt 3), 944-956. https://doi.org/10.1093/brain/awt010
Engel, A. G. (2018). Congenital Myasthenic syndromes in 2018. Current Neurology and Neuroscience Reports, 18(8), 46. https://doi.org/10.1007/s11910-018-0852-4
Gao, X. D., Moriyama, S., Miura, N., Dean, N., & Nishimura, S. (2008). Interaction between the C termini of Alg13 and Alg14 mediates formation of the active UDP-N-acetylglucosamine transferase complex. Journal of Biological Chemistry, 283(47), 32534-32541. https://doi.org/10.1074/jbc.M804060200
Gao, X. D., Tachikawa, H., Sato, T., Jigami, Y., & Dean, N. (2005). Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum to form a novel bipartite UDP-N-acetylglucosamine transferase required for the second step of N-linked glycosylation. Journal of Biological Chemistry, 280(43), 36254-36262. https://doi.org/10.1074/jbc.M507569200
Kvarnung, M., Taylan, F., Nilsson, D., Anderlid, B. M., Malmgren, H., Lagerstedt-Robinson, K., Holmberg, E., Burstedt, M., Nordenskjöld, M., Nordgren, A., & Lundberg, E. S. (2018). Genomic screening in rare disorders: New mutations and phenotypes, highlighting ALG14 as a novel cause of severe intellectual disability. Clinical Genetics, 94(6), 528-537. https://doi.org/10.1111/cge.13448
Liewluck, T., Selcen, D., & Engel, A. G. (2011). Beneficial effects of albuterol in congenital endplate acetylcholinesterase deficiency and Dok-7 myasthenia. Muscle & Nerve, 44(5), 789-794. https://doi.org/10.1002/mus.22176
Palombo, F., Piccolo, B., Saccani, E., Fiorini, C., Capristo, M., Caporali, L., Pisani, F., & Carelli, V. (2021). A novel ALG14 missense variant in an alive child with myopathy, epilepsy, and progressive cerebral atrophy. American Journal of Medical Genetics. Part A, 185, 1918-1921. https://doi.org/10.1002/ajmg.a.62153
Schorling, D. C., Rost, S., Lefeber, D. J., Brady, L., Muller, C. R., Korinthenberg, R., Tarnopolsky, M., Bönnemann, C. G., Rodenburg, R. J., Bugiani, M., Beytia, M., Krüger, M., van der Knaap, M., & Kirschner, J. (2017). Early and lethal neurodegeneration with myasthenic and myopathic features: A new ALG14-CDG. Neurology, 89(7), 657-664. https://doi.org/10.1212/WNL.0000000000004234
Scott, K., Gadomski, T., Kozicz, T., & Morava, E. (2014). Congenital disorders of glycosylation: New defects and still counting. Journal of Inherited Metabolic Disease, 37(4), 609-617. https://doi.org/10.1007/s10545-014-9720-9
Takayama, J., Tadaka, S., Yano, K., Katsuoka, F., Gocho, C., Funayama, T., Makino, S., Okamura, Y., Kikuchi, A., Sugimoto, S., Kawashima, J., Otsuki, A., Sakurai-Yageta, M., Yasuda, J., Kure, S., Kinoshita, K., Yamamoto, M., & Tamiya, G. (2021). Construction and integration of three de novo Japanese human genome assemblies toward a population-specific reference. Nature Communications, 12(1), 226. https://doi.org/10.1038/s41467-020-20146-8
Troha Gergeli, A., Neubauer, D., Golli, T., Butenko, T., Loboda, T., Maver, A., & Osredkar, D. (2020). Prevalence and genetic subtypes of congenital myasthenic syndromes in the pediatric population of Slovenia. European Journal of Paediatric Neurology, 26, 34-38. https://doi.org/10.1016/j.ejpn.2020.02.002
Wada, Y. (2016). Mass spectrometry of transferrin and apolipoprotein C-III for diagnosis and screening of congenital disorder of glycosylation. Glycoconjugate Journal, 33(3), 297-307. https://doi.org/10.1007/s10719-015-9636-0