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Novel PCNT variants in MOPDII with attenuated growth restriction and pachygyria.
Clin Genet. 2020 09; 98(3):282-287.CG

Abstract

Biallelic loss-of-function mutations in the centrosomal pericentrin gene (PCNT) cause microcephalic osteodysplastic primordial dwarfism type II (MOPDII), which is characterized by extreme growth retardation, microcephaly, skeletal dysplasia, and dental anomalies. Life expectancy is reduced due to a high risk of cerebral vascular anomalies. Here, we report two siblings with MOPDII and attenuated growth restriction, and pachygyria. Compound heterozygosity for two novel truncated PCNT variants was identified. Both truncated PCNT proteins were expressed in patient's fibroblasts, with a reduced total protein amount compared to control. Patient's fibroblasts showed impaired cell cycle progression. As a novel finding, 20% of patient's fibroblasts were shown to express PCNT comparable to control. This was associated with normal mitotic morphology and normal co-localization of mutated PCNT with centrosome-associated proteins γ-tubulin and centrin 3, suggesting some residual function of truncated PCNT proteins. These data expand the clinical and molecular spectrum of MOPDII and indicate that residual PCNT function might be associated with attenuated growth restriction in MOPDII.

Authors+Show Affiliations

Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria. Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergology and Endocrinology, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria. Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.Institute of Legal Medicine, Medical University of Innsbruck, Innsbruck, Austria. Forensic Science Program, The Pennsylvania State University, University Park, Pennsylvania, USA.Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergology and Endocrinology, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.Division of Cell Biology, Medical University of Innsbruck, Innsbruck, Austria.Department of Pediatrics I, Medical University of Innsbruck, Innsbruck, Austria.Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmonology, Allergology and Endocrinology, Comprehensive Center for Pediatrics, Medical University of Vienna, Vienna, Austria.

Pub Type(s)

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

Language

eng

PubMed ID

32557621

Citation

Waich, Stephanie, et al. "Novel PCNT Variants in MOPDII With Attenuated Growth Restriction and Pachygyria." Clinical Genetics, vol. 98, no. 3, 2020, pp. 282-287.
Waich S, Janecke AR, Parson W, et al. Novel PCNT variants in MOPDII with attenuated growth restriction and pachygyria. Clin Genet. 2020;98(3):282-287.
Waich, S., Janecke, A. R., Parson, W., Greber-Platzer, S., Müller, T., Huber, L. A., Valovka, T., & Vodopiutz, J. (2020). Novel PCNT variants in MOPDII with attenuated growth restriction and pachygyria. Clinical Genetics, 98(3), 282-287. https://doi.org/10.1111/cge.13797
Waich S, et al. Novel PCNT Variants in MOPDII With Attenuated Growth Restriction and Pachygyria. Clin Genet. 2020;98(3):282-287. PubMed PMID: 32557621.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel PCNT variants in MOPDII with attenuated growth restriction and pachygyria. AU - Waich,Stephanie, AU - Janecke,Andreas R, AU - Parson,Walther, AU - Greber-Platzer,Susanne, AU - Müller,Thomas, AU - Huber,Lukas A, AU - Valovka,Taras, AU - Vodopiutz,Julia, Y1 - 2020/07/07/ PY - 2020/05/18/received PY - 2020/06/06/revised PY - 2020/06/10/accepted PY - 2020/6/20/pubmed PY - 2021/7/13/medline PY - 2020/6/20/entrez KW - MOPDII KW - microcephalic osteodysplastic primordial dwarfism type II KW - normal mitotic morphology KW - pachygyria KW - pericentrin SP - 282 EP - 287 JF - Clinical genetics JO - Clin Genet VL - 98 IS - 3 N2 - Biallelic loss-of-function mutations in the centrosomal pericentrin gene (PCNT) cause microcephalic osteodysplastic primordial dwarfism type II (MOPDII), which is characterized by extreme growth retardation, microcephaly, skeletal dysplasia, and dental anomalies. Life expectancy is reduced due to a high risk of cerebral vascular anomalies. Here, we report two siblings with MOPDII and attenuated growth restriction, and pachygyria. Compound heterozygosity for two novel truncated PCNT variants was identified. Both truncated PCNT proteins were expressed in patient's fibroblasts, with a reduced total protein amount compared to control. Patient's fibroblasts showed impaired cell cycle progression. As a novel finding, 20% of patient's fibroblasts were shown to express PCNT comparable to control. This was associated with normal mitotic morphology and normal co-localization of mutated PCNT with centrosome-associated proteins γ-tubulin and centrin 3, suggesting some residual function of truncated PCNT proteins. These data expand the clinical and molecular spectrum of MOPDII and indicate that residual PCNT function might be associated with attenuated growth restriction in MOPDII. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/32557621/Novel_PCNT_variants_in_MOPDII_with_attenuated_growth_restriction_and_pachygyria_ L2 - https://doi.org/10.1111/cge.13797 DB - PRIME DP - Unbound Medicine ER -