Congenital myasthenic syndrome with respiratory failure type 20

Congenital myasthenic presynaptic syndrome type 20 - neuromuscular disease with autosomal recessive inheritance caused by homozygous or compound heterozygous mutations in the SLC5A7 gene, characterized by severe hypotonia associated with episodic apnea soon after birth of the child. This article describes the case of SLC5A7 gene mutation detection in girl (age 5 month) with respiratory failure, hypoxic-ischemic encephalopathy, severe muscle hypotonia. The previously described homozygous variant of the nucleotide sequence in the 6 exon of the SLC5A7 gene (p.Ile291Thr) was detected by whole-exome sequencing. This mutation was validated by the Sanger sequencing method in patients. The mother of the child has a mutation in the heterozygous state, the father has no the same mutation. One cannot exclude the presence of gonadal mosaicism and/or «false paternity» in the father in view of the presence of a homozygous mutation in the child and the absence of a second mutation in the parents. The presented clinical observation of a patient with a rare genetic form of myasthenia with respiratory failure shows the importance of DNA diagnostics using the method of whole-exome sequencing in order to search for a molecular defect and to determine the further option of patients management with this severe pathology.

ген SLC5A7, врожденный миастенический синдром, дыхательная недостаточность, мышечная гипотония, полноэкзомное секвенирование, SLC5A7 gene, congenital myasthenic syndrome, respiratory failure, muscle hypotonia, whole-exome sequencing

1. Агафонов Б.В., Котов С.В., Сидорова О.П. «Миастения и врожденные миастенические синдромы» - 2013. Медицинское информационное агентство. - М. - 224с.

2. Abicht A., Muller J., Lochmuller Н. Congenital Myasthenic Syndromes. GeneReviews® [Internet]. 2016

3. Black, S.A., and Rylett, R.J. Choline transporter CHT regulation and function in cholinergic neurons. Cent. Nerv. Syst. Agents Med. Chem.2012;12:114-121.

4. Haga, T. Molecular properties of the high-affinity choline transporter CHT1. J. Biochem. 2014;156:181-194.

5. Engel, A.G., Shen, X.M., Selcen, D., and Sine, S.M. Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment. Lancet Neurol. 2015;14:420-434.

6. Byring, R.F., Pihko, H., Tsujino, A., Shen, X.M., Gustafsson, B., Hackman, P., Ohno, K., Engel,A.G. and Udd,B. Congenital myasthenic syndrome associated with episodic apnea and sudden infant death. Neuromuscul. Disord. 2002;12:548-553.

7. Ohno, K., Tsujino, A., Brengman, J.M., Harper, C.M., Bajzer, Z., Udd, B., Beyring, R., Robb, S., Kirkham, F.J., and Engel, A.G. Choline acetyltransferase mutations cause myasthenic syndrome associated with episodic apnea in humans. Proc. Natl. Acad. Sci. 2001;98:2017-2022.

8. База данных OMIM - https://www.omim.org/entry/617143.

9. База данных Orphanet - https://www.orpha.net.

10. Bauche, S., O’Regan, S., Azuma, Y., Laffargue, F., McMacken, G., Sternberg, D., Brochier, G., Buon, C., Bouzidi, N., Topf, A., Lacene, E., Remerand, G. Impaired presynaptic high-affinity choline transporter causes a congenital myasthenic syndrome with episodic apnea. Am. J. Hum. Genet. 2016;99:753-761.

11. McMacken G., Whittaker R., Evangelista T., Abicht А., Dus М., Lochmuller Н. Congenital myasthenic syndrome with episodic apnoea: clinical, neurophysiological and genetic features in the long-term follow-up of 19 patients. J Neurol. 2018; 265(1): 194-203.

12. Wang H., Salter C., Refai O., Hardy H., Barwick K., Akpulat U., Kvarnung M., Chioza B., Harlalka G., Taylan F., Sejersen T., Wright J., Zimmerman H., Karakaya M., Stuve B., Weis J., Schara U., Russell M., Abdul-Rahman O., Chilton J., Blakely R., Baple E., Cirak S., Crosby A. Choline transporter mutations in severe congenital myasthenic syndrome disrupt transporter localization. Brain. 2017;140(11):2838-2850.