Pergande, Matthias, Motameny, Susanne, Oezdemir, Oezkan, Kreutzer, Mona, Wang, Haicui, Daimagueler, Huelya-Sevcan, Becker, Kerstin, Karakaya, Mert, Ehrhardt, Harald ORCID: 0000-0003-4587-1734, Elcioglu, Nursel, Ostojic, Slavica, Chao, Cho-Ming, Kawalia, Amit, Duman, Ozgur, Koy, Anne, Hahn, Andreas, Reimann, Jens, Schoner, Katharina, Schaenzer, Anne, Westhoff, Jens H., Schwaibold, Eva Maria Christina, Cossee, Mireille, Imbert-Bouteille, Marion, von Pein, Harald, Haliloglu, Goknur, Topaloglu, Haluk, Altmueller, Janine, Nuernberg, Peter, Thiele, Holger ORCID: 0000-0002-0169-998X, Heller, Raoul and Cirak, Sebahattin (2020). The genomic and clinical landscape of fetal akinesia. Genet. Med., 22 (3). S. 511 - 524. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0366

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Abstract

Purpose Fetal akinesia has multiple clinical subtypes with over 160 gene associations, but the genetic etiology is not yet completely understood. Methods In this study, 51 patients from 47 unrelated families were analyzed using next-generation sequencing (NGS) techniques aiming to decipher the genomic landscape of fetal akinesia (FA). Results We have identified likely pathogenic gene variants in 37 cases and report 41 novel variants. Additionally, we report putative pathogenic variants in eight cases including nine novel variants. Our work identified 14 novel disease-gene associations for fetal akinesia: ADSSL1, ASAH1, ASPM, ATP2B3, EARS2, FBLN1, PRG4, PRICKLE1, ROR2, SETBP1, SCN5A, SCN8A, and ZEB2. Furthermore, a sibling pair harbored a homozygous copy-number variant in TNNT1, an ultrarare congenital myopathy gene that has been linked to arthrogryposis via Gene Ontology analysis. Conclusion 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Pergande, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Motameny, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oezdemir, OezkanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreutzer, MonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, HaicuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Daimagueler, Huelya-SevcanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, KerstinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karakaya, MertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ehrhardt, HaraldUNSPECIFIEDorcid.org/0000-0003-4587-1734UNSPECIFIED
Elcioglu, NurselUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ostojic, SlavicaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chao, Cho-MingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kawalia, AmitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Duman, OzgurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koy, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hahn, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reimann, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoner, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schaenzer, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Westhoff, Jens H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwaibold, Eva Maria ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cossee, MireilleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Imbert-Bouteille, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Pein, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haliloglu, GoknurUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Topaloglu, HalukUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuernberg, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thiele, HolgerUNSPECIFIEDorcid.org/0000-0002-0169-998XUNSPECIFIED
Heller, RaoulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cirak, SebahattinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-343308
DOI: 10.1038/s41436-019-0680-1
Journal or Publication Title: Genet. Med.
Volume: 22
Number: 3
Page Range: S. 511 - 524
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1530-0366
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DISTAL ARTHROGRYPOSIS; NEMALINE MYOPATHY; MUTATIONS; GENETICS; VARIANTSMultiple languages
Genetics & HeredityMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34330

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