University of Oulu

Mäkitie RE, Niinimäki T, Suo-Palosaari M, Kämpe A, Costantini A, Toiviainen-Salo S, Niinimäki J and Mäkitie O (2020) PLS3 Mutations Cause Severe Age and Sex-Related Spinal Pathology. Front. Endocrinol. 11:393. doi: 10.3389/fendo.2020.0039

PLS3 mutations cause severe age and sex-related spinal pathology

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Author: Mäkitie, Riikka E.1,2,3; Niinimäki, Tuukka4; Suo-Palosaari, Maria5,6;
Organizations: 1Folkhälsan Institute of Genetics, Helsinki, Finland
2Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
3Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, United Kingdom
4Department of Surgery, Oulu University Hospital, Oulu, Finland
5Research Unit of Medical Imaging, Physics and Technology, University of Oulu, Oulu, Finland
6Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
7Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, and Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
8Department of Pediatric Radiology, Medical Imaging Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
9Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Frontiers Media, 2020
Publish Date: 2020-10-19


Objective: Mutations in the X-chromosomal PLS3-gene, encoding Plastin 3, lead to severe early-onset osteoporosis, suggesting a major role for PLS3 in bone metabolism. However, the consequences of abnormal PLS3 function in bone and other tissues remain incompletely characterized. This study evaluated spinal consequences of aberrant PLS3 function in patients with PLS3 mutations.

Design: A cross-sectional cohort study with spinal magnetic resonance imaging of 15 PLS3 mutation-positive (age range 9–77 years) and 13 mutation-negative (9–70 years) subjects. Images were reviewed for spinal alignment, vertebral heights and morphology, intervertebral disc changes and possible endplate deterioration.

Results: Vertebral changes were significantly more prevalent in the mutation-positive subjects compared with the mutation-negative subjects; they were most abundant in upper thoracic spine, and in all age groups and both sexes, although more prominent in males. Difference in anterior vertebral height reduction was most significant in T5 and T6 (p = 0.046 and p = 0.041, respectively). Mid-vertebral height reduction was most significant in T3 and T5 (p = 0.037 and p = 0.005, respectively), and, for male mutation-positive subjects only, in T4 and T6–10 (p = 0.005–0.030 for each vertebra). Most of the abnormal vertebrae were biconcave in shape but thoracic kyphosis or lumbar lordosis were unchanged. Vertebral endplates were well-preserved in the mutation-positive subjects with even fewer Schmorl nodes than the mutation-negative subjects (10 vs. 16).

Conclusions: Compromised PLS3 function introduces severe and progressive changes to spinal structures that are present already in childhood, in both sexes and most abundant in upper thoracic spine. Cartilaginous structures are well-preserved.

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Series: Frontiers in endocrinology
ISSN: 1664-2392
ISSN-E: 1664-2392
ISSN-L: 1664-2392
Volume: 11
Article number: 393
DOI: 10.3389/fendo.2020.00393
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
Funding: This study was supported by the Sigrid Jusélius Foundation, the Folkhälsan Research Foundation, the Academy of Finland, the Foundation for Pediatric Research, the Helsinki University Research Funds, Helsinki University and Helsinki University Hospital through the Doctoral Programme in Clinical Research, the Orion Research Foundation, the Finnish ORL–HNS Foundation, the Päivikki and Sakari Sohlberg Foundation, the Finnish–Norwegian Medical Foundation, the Jalmari and Rauha Ahokas Foundation, the Juhani Aho Foundation, the Swedish Research Council, the Novo Nordisk Foundation, the European Society for Pediatric Endocrinology Research Unit, the Swedish Childhood Cancer Foundation, and through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet. The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Copyright information: © 2020 Mäkitie, Niinimäki, Suo-Palosaari, Kämpe, Costantini, Toiviainen-Salo, Niinimäki and Mäkitie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.