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A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys.
Clin Genet. 2018 10; 94(3-4):303-312.CG

Abstract

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.

Authors+Show Affiliations

Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.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.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.Division of Genetics/Dysmorphology, Department of Pediatrics, University of New Mexico School of Medicine, Albuquerque, New Mexico.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29851065

Citation

Ito, Y A., et al. "A ZPR1 Mutation Is Associated With a Novel Syndrome of Growth Restriction, Distinct Craniofacial Features, Alopecia, and Hypoplastic Kidneys." Clinical Genetics, vol. 94, no. 3-4, 2018, pp. 303-312.
Ito YA, Smith AC, Kernohan KD, et al. A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys. Clin Genet. 2018;94(3-4):303-312.
Ito, Y. A., Smith, A. C., Kernohan, K. D., Pena, I. A., Ahmed, A., McDonell, L. M., Beaulieu, C., Bulman, D. E., Smidt, A., Sawyer, S. L., Dyment, D. A., Boycott, K. M., & Clericuzio, C. L. (2018). A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys. Clinical Genetics, 94(3-4), 303-312. https://doi.org/10.1111/cge.13388
Ito YA, et al. A ZPR1 Mutation Is Associated With a Novel Syndrome of Growth Restriction, Distinct Craniofacial Features, Alopecia, and Hypoplastic Kidneys. Clin Genet. 2018;94(3-4):303-312. PubMed PMID: 29851065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A ZPR1 mutation is associated with a novel syndrome of growth restriction, distinct craniofacial features, alopecia, and hypoplastic kidneys. AU - Ito,Y A, AU - Smith,A C, AU - Kernohan,K D, AU - Pena,I A, AU - Ahmed,A, AU - McDonell,L M, AU - Beaulieu,C, AU - Bulman,D E, AU - Smidt,A, AU - Sawyer,S L, AU - ,, AU - Dyment,D A, AU - Boycott,K M, AU - Clericuzio,C L, Y1 - 2018/06/29/ PY - 2018/03/02/received PY - 2018/05/24/revised PY - 2018/05/27/accepted PY - 2018/6/1/pubmed PY - 2019/10/29/medline PY - 2018/6/1/entrez KW - ZPR1 KW - alopecia KW - cell cycle progression KW - exome sequencing KW - growth restriction KW - kidney KW - zinc finger SP - 303 EP - 312 JF - Clinical genetics JO - Clin. Genet. VL - 94 IS - 3-4 N2 - 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. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/29851065/A_ZPR1_mutation_is_associated_with_a_novel_syndrome_of_growth_restriction_distinct_craniofacial_features_alopecia_and_hypoplastic_kidneys_ L2 - https://doi.org/10.1111/cge.13388 DB - PRIME DP - Unbound Medicine ER -