Résumé :
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IntroductionRecently, neuromuscular junction (NMJ) genes have been implicated in FADS, mainly in multiple pterygium syndromes, lethal (LMPS) or not (Escobar syndrome). Recessive mutations have been identified in CHRNG, RAPSN, CHRND, CHRNA1 and DOK7. Patients and MethodsWe received 48 patients with FADS, for analysis of NMJ genes. Of these patients, 15 were alive and had arthrogryposis (+/- ptgiums), 28 foetuses had FADS leading to pregnancy termination or who died in utero, and 5 patients died in the first year.Analysis of CHRNG, RAPSN, CHRND, CHRNA1 and DOK7 genes were undertaken, using PCR-sequencing, in order to (i) determine etiological diagnosis (ii), estimate the frequency of NMJ dysfunction and (iii) try to determine genotype-phenotype correlation. Preliminary resultsThree patients were identified with bi-allelic mutations of CHRNG, coding for the foetal sub-unit of the acetylcholine receptor. Two of these patients were diagnosed with Escobar syndrome and one foetus had LMPS leading to pregnancy termination at 13 weeks of gestation. Different types of mutations were identified: stop, splice or frameshift, either at homozygous or compound heterozygous state.A heterozygous frameshift mutation of DOK7 was identified in a foetus with FADS and ptgiums, leading to termination of pregnancy at 22 weeks. Studies are ongoing to find a second mutation. Conclusions and PerspectivesTo this point, sequencing of NMJ genes in our cohort has a yield of 8 % of positive diagnoses (studies are still underway). Genetic confirmation is important for genetic counselling. Up to date, the diagnostic algorithm remains unclear in FADS.
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