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001-es BibID:	BIBFORM066488
035-os BibID:	(WoS)000394114500021 (Scopus)84978036042
Első szerző:	Paulussen, Aimee D. C.
Cím:	Rare novel variants in the ZIC3 gene cause X-linked heterotaxy / Aimee D. C. Paulussen, Anja Steyls, Jo Vanoevelen, Florence H. J. van Tienen, Ingrid P. C. Krapels, Godelieve R. F. Claes, Sonja Chocron, Crool Velter, Gita M. Tan-Sindhunata, Catarina Lundin, Irene Valenzuela, Balint Nagy, Iben Bache, Lisa Leth Maroun, Kristiina Avela, Han G. Brunner, Hubert J. M. Smeets, Jeroen Bakkers, Arthur van den Wijngaard
Dátum:	2016
ISSN:	1018-4813
Megjegyzések:	Variants in the ZIC3 gene are rare, but have demonstrated their profound clinical significance in X-linked heterotaxy, affecting in particular male patients with abnormal arrangement of thoracic and visceral organs. Several reports have shown relevance of ZIC3 gene variants in both familial and sporadic cases and with a predominance of mutations detected in zinc-finger domains. No studies so far have assessed the functional consequences of ZIC3 variants in an in vivo model organism. A study population of 348 patients collected over more than 10 years with a large variety of congenital heart disease including heterotaxy was screened for variants in the ZIC3 gene. Functional effects of three variants were assessed both in vitro and in vivo in the zebrafish. We identified six novel pathogenic variants (1,7%), all in either male patients with heterotaxy (n=5) or a female patient with multiple male deaths due to heterotaxy in the family (n=1). All variants were located within the zinc-finger domains or leading to a truncation before these domains. Truncating variants showed abnormal trafficking of mutated ZIC3 proteins, whereas the missense variant showed normal trafficking. Overexpression of wild-type and mutated ZIC protein in zebrafish showed full non-functionality of the two frame-shift variants and partial activity of the missense variant compared with wild-type, further underscoring the pathogenic character of these variants. Concluding, we greatly expanded the number of causative variants in ZIC3 and delineated the functional effects of three variants using in vitro and in vivo model systems.
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk heterotaxy congenital heart defects ZIC3 X-linked gene
Megjelenés:	European Journal Of Human Genetics. - 24 : 12 (2016), p. 1783-1791. -
További szerzők:	Steyls, Anja Vanoevelen, Jo van Tienen, Florence H. J. Krapels, Ingrid P. C. Claes, Godelieve R. F. Chocron, Sonja Velter, Crool Tan-Sindhunata, Gita M. Lundin, Catarina Valenzuela, Irene Nagy Bálint (1956-) (molekuláris genetikus) Bache, Iben Maroun, Lisa Leth Avela, Kristiina Brunner, Han G. Smeets, Hubert J. M. Bakkers, Jeroen van den Wijngaard, Arthur
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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