The genomic and clinical landscape of fetal akinesia.
Matthias PergandeSusanne MotamenyÖzkan ÖzdemirMona KreutzerHaicui WangHülya-Sevcan DaimagülerKerstin BeckerMert KarakayaHarald EhrhardtNursel ElciogluSlavica OstojicCho-Ming ChaoAmit KawaliaÖzgür DumanAnne KoyAndreas HahnJens ReimannKatharina SchonerAnne SchänzerJens H WesthoffEva Maria Christina SchwaiboldMireille CosseeMarion Imbert-BouteilleHarald von PeinGöknur HalilogluHaluk TopalogluJanine AltmüllerPeter NürnbergHolger ThieleRaoul HellerSebahattin ÇırakPublished in: Genetics in medicine : official journal of the American College of Medical Genetics (2019)
Our analysis indicates that genetic defects leading to primary skeletal muscle diseases might have been underdiagnosed, especially pathogenic variants in RYR1. We discuss three novel putative fetal akinesia genes: GCN1, IQSEC3 and RYR3. Of those, IQSEC3, and RYR3 had been proposed as neuromuscular disease-associated genes recently, and our findings endorse them as FA candidate genes. By combining NGS with deep clinical phenotyping, we achieved a 73% success rate of solved cases.