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Congenital myasthenic syndrome due to novel CHAT mutations in an ethnic kadazandusun family
Joo-San Tan BSc1, Tomica Ambang BSc1, Azlina Ahmad-Annuar PhD2, Giri Shan Rajahram MRCP3, Kum Thong Wong FRCPath, MD4 andKhean Jin Goh FRCP1,*
Article first published online: 23 MAR 2016 DOI: 10.1002/mus.25037
ABSTRACT
Muscle Nerve, 2016
- Introduction
Choline acetyltransferase (CHAT) gene mutations cause a rare presynaptic congenital myasthenic syndrome due to impaired acetylcholine resynthesis.
- Methods
We report 2 Kadazandusun brothers with novel heterozygous CHAT mutations.
- Results
The siblings were from a family of 7 children of nonconsanguineous parents, 3 who died from apneic crises. Both presented in infancy with ptosis and exertional limb weakness, but only 1 apnea episode was reported in the older sibling. The elder brother had a positive edrophonium test, and both were negative for acetylcholine receptor antibodies but improved with pyridostigmine treatment. A subsequent repetitive nerve stimulation test showed marked decremental response in the abductor digiti minimi only after prolonged ulnar nerve stimulation. Two novel CHAT gene mutations, p.Val306Leu and p.Ser704del were detected; the parents carried 1 mutation each.
- Conclusions
Differences in survival demonstrate phenotypic variability within the same family and a relatively good long-term outcome of the surviving siblings.
Pour plus de compréhension voici ce qu'est CHAT : C'est le gène qui code la choline acétyltransférase (ChAT) l'enzyme principale de la synthèse de l'acétylcholine, un important neurotransmetteur des systèmes nerveux central et périphérique. La ChAT qui est une enzyme de type acyltransférase, est synthétisée dans le corps cellulaire des neurones puis transféré par le flux axoplasmique vers la terminaison axonale où elle métabolise l'actéycholine à partir de la choline et d'un acétate fournit par l'acétyl-coenzyme A.
Chez l'homme, cette enzyme est codée par le gène CHAT situé sur le chromosome 10 humain dont les mutations sont à l'origine de myasthénies sévères congénitales.