A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys.

Autor: Ito YA; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Smith AC; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Kernohan KD; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Pena IA; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Ahmed A; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., McDonell LM; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Beaulieu C; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Bulman DE; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Smidt A; Division of Genetics/Dysmorphology, Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico.; Department of Dermatology, University of New Mexico School of Medicine, Albuquerque, New Mexico., Sawyer SL; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Dyment DA; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Boycott KM; Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada., Clericuzio CL; Division of Genetics/Dysmorphology, Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2018 Oct; Vol. 94 (3-4), pp. 303-312. Date of Electronic Publication: 2018 Jun 29.
DOI: 10.1111/cge.13388
Abstrakt: A novel autosomal recessive disorder characterized by pre- and postnatal growth restriction with microcephaly, distinctive craniofacial features, congenital alopecia, hypoplastic kidneys with renal insufficiency, global developmental delay, severe congenital sensorineural hearing loss, early mortality, hydrocephalus, and genital hypoplasia was observed in 4 children from 3 families of New Mexican Hispanic heritage. Three of the children died before 3 years of age from uremia and/or sepsis. Exome sequencing of the surviving individual identified a homozygous c.587T>C (p.Ile196Thr) mutation in ZPR1 Zinc Finger (ZPR1) that segregated appropriately in her family. In a second family, the identical variant was shown to be heterozygous in the affected individual's parents and not homozygous in any of her unaffected siblings. ZPR1 is a ubiquitously expressed, highly conserved protein postulated to transmit proliferative signals from the cell membrane to the nucleus. Structural modeling reveals that p.Ile196Thr disrupts the hydrophobic core of ZPR1. Patient fibroblast cells showed no detectable levels of ZPR1 and the cells showed a defect in cell cycle progression where a significant number of cells remained arrested in the G1 phase. We provide genetic and molecular evidence that a homozygous missense mutation in ZPR1 is associated with a rare and recognizable multisystem syndrome.
(© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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