Emergence of osteolysis as a new radiological feature in a case with a novel BMP2 gene variant
-
Suzan Süncak
,
Merve Berfin Aktan Karaca
Abstract
Objectives
Bone morphogenetic protein 2 (BMP2) is essential for endochondral ossification, skeletal development, and bone homeostasis. Monoallelic loss-of-function variants in BMP2 have been linked to short stature, facial dysmorphism, and skeletal anomalies, often accompanied by cardiac involvement. Here, we describe a 10-year-old girl with a novel heterozygous truncating BMP2 variant, presenting with distinct facial features, short stature, and skeletal abnormalities, notably osteolysis in the phalanges.
Case presentation
The patient was initially evaluated at six months of age due to hypotonia and dysmorphic facial features. At 10 years old, she presented with short stature and skeletal radiographs revealed osteolysis in multiple phalanges. Additional clinical evaluations, including echocardiography and metabolic studies, were unremarkable. Whole-exome sequencing identified a de novo heterozygous truncating variant (c.440C>G; p.Ser147*) in BMP2.
Conclusions
This report identifies a novel BMP2 nonsense variant and introduces osteolysis as a previously unrecognized phenotype. These findings highlight the necessity of longitudinal skeletal monitoring in BMP2-related conditions and underscore the importance of genetic evaluation in patients with subtle skeletal dysplasias to facilitate early diagnosis and management.
Acknowledgments
Suzan Süncak, MD is the corresponding author of this study. I would like to extend my sincere thanks to my professors and colleagues who supported me in preparing this case article.
-
Research ethics: Since this study is a case study examining patient data, no Ethics Committee approval was required. Written consent was obtained from the patients’ parents for the use of their medical data and photographs.
-
Informed consent: Informed consent was obtained from the patient’s parents included in this study.
-
Author contributions: Suzan Süncak: Reviewing the literature, data collection, writing the original draft. Merve Berfin Aktan: Data collection, writing. Semra Gürsoy: Confirming genetic analysis, reviewing, editing the draft. Mehmet Kocabey: Interpreting genetic tests, editing the draft. Korcan Demir: Initial assessment of the case, refer the genetic department, editing the original draft. Fatma Ceren Sarioğlu: Interpreting skeletal survey. Ayfer Ülgenalp and Özlem Giray Bozkaya: Literature review, final approval, editing the draft.
-
Use of Large Language Models, AI and Machine Learning Tools: Not applicable.
-
Conflict of interest: The authors state no conflict of interest.
-
Research funding: None declared.
-
Data availability: The datasets for this article are not publicly available due to concerns regarding participant/patient anonymity.
References
1. Miyazono, K, Kamiya, Y, Morikawa, M. Bone morphogenetic protein receptors and signal transduction. J Biochem 2010;147:35–51. https://doi.org/10.1093/jb/mvp148.Suche in Google Scholar PubMed
2. Wang, RN, Green, J, Wang, Z, Deng, Y, Qiao, M, Peabody, M, et al.. Bone Morphogenetic Protein (BMP) signaling in development and human diseases. Genes Dis 2014;1:87–105. https://doi.org/10.1016/j.gendis.2014.07.005.Suche in Google Scholar PubMed PubMed Central
3. Mueller, TD, Nickel, J. Promiscuity and specificity in BMP receptor activation. FEBS Lett 2012;586:1846e1859. https://doi.org/10.1016/j.febslet.2012.02.043.Suche in Google Scholar PubMed
4. Richards, S, Aziz, N, Bale, S, Bick, D, Das, S, Gastier-Foster, J, ACMG Laboratory Quality Assurance Committee, et al.. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med 2015;17:405–24. https://doi.org/10.1038/gim.2015.30.Suche in Google Scholar PubMed PubMed Central
5. Heubel, B, Nohe, A. The role of BMP signaling in osteoclast regulation. J Dev Biol 2021;9:24. https://doi.org/10.3390/jdb9030024.Suche in Google Scholar PubMed PubMed Central
6. Halloran, D, Durbano, HW, Nohe, A. Bone morphogenetic protein-2 in development and bone homeostasis. J Dev Biol 2020;8:19. https://doi.org/10.3390/jdb8030019.Suche in Google Scholar PubMed PubMed Central
7. Tan, TY, Gonzaga-Jauregui, C, Bhoj, EJ, Strauss, KA, Brigatti, K, Puffenberger, E, et al.. Monoallelic BMP2 variants predicted to result in haploinsufficiency cause craniofacial, skeletal, and cardiac features overlapping those of 20p12 deletions. Am J Hum Genet 2017;101:985–94. https://doi.org/10.1016/j.ajhg.2017.10.006.Suche in Google Scholar PubMed PubMed Central
8. Mishra, R, Jain, V, Gupta, D, Saxena, R, Kulshreshtha, S, Ramprasad, VL, et al.. Robinow syndrome and brachydactyly: an interplay of high-throughput sequencing and deep phenotyping in a kindred. Mol Syndromol 2020;11:43–9. https://doi.org/10.1159/000505506.Suche in Google Scholar PubMed PubMed Central
9. Priestley, JRC, Deshwar, AR, Murthy, H, D’Agostino, MD, Dupuis, L, Gangaram, B, et al.. Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum. Genet Med 2023;25:100863. https://doi.org/10.1016/j.gim.2023.100863.Suche in Google Scholar PubMed
10. Bessa, PC, Pedro, AJ, Klösch, B, Nobre, A, van Griensven, M, Reis, RL, et al.. Osteoinduction in human fat-derived stem cells by recombinant human bone morphogenetic protein-2 produced in Escherichia coli. Biotechnol Lett 2008;30:15–21. https://doi.org/10.1007/s10529-007-9501-8.Suche in Google Scholar PubMed
© 2025 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Editorial
- Sunlight, supplements, and science: vitamin D as a tool for pediatric health care
- Mini Review
- Physical activity and vitamin D in children: a review of impacts on bone health and fitness
- Original Articles
- Association between overweight or obesity and vitamin D status in preschool children: an epidemiological survey in Beijing, China, 2021–2023
- Association between partial remission phase in type 1 diabetes and vitamin D receptor Fok1 rs2228570 polymorphism
- Optimal vitamin D status for Chinese infants in Hong Kong: insights from the relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels
- Reviews
- The changing landscape in the evaluation of hypotonic polyuria in children and adolescents: the role of the new copeptin stimulation tests
- A systematic review and meta-analysis of the self-reported Pubertal Development Scale’s applicability to children
- Original Articles
- Assessing prediabetes and cardiometabolic risk in Danish youth with obesity
- Endocrinopathies in children with inborn errors of immunity: a single-center experience
- Relationship between blood lipids and bone mineral density in healthy preschoolers: a 12-month cohort study
- The causal role of endocrine disrupting chemicals in pubertal timing: a Mendelian randomization study
- Case Reports
- Vitamin D dependent rickets type 2A: a case series of two siblings with novel mutation in vitamin D receptor gene responded to high dose oral calcium and calcitriol
- Emergence of osteolysis as a new radiological feature in a case with a novel BMP2 gene variant
- Rare case of ACTH-independent Cushing syndrome: diagnostic challenges and management
Artikel in diesem Heft
- Frontmatter
- Editorial
- Sunlight, supplements, and science: vitamin D as a tool for pediatric health care
- Mini Review
- Physical activity and vitamin D in children: a review of impacts on bone health and fitness
- Original Articles
- Association between overweight or obesity and vitamin D status in preschool children: an epidemiological survey in Beijing, China, 2021–2023
- Association between partial remission phase in type 1 diabetes and vitamin D receptor Fok1 rs2228570 polymorphism
- Optimal vitamin D status for Chinese infants in Hong Kong: insights from the relationship between serum 25-hydroxyvitamin D and parathyroid hormone levels
- Reviews
- The changing landscape in the evaluation of hypotonic polyuria in children and adolescents: the role of the new copeptin stimulation tests
- A systematic review and meta-analysis of the self-reported Pubertal Development Scale’s applicability to children
- Original Articles
- Assessing prediabetes and cardiometabolic risk in Danish youth with obesity
- Endocrinopathies in children with inborn errors of immunity: a single-center experience
- Relationship between blood lipids and bone mineral density in healthy preschoolers: a 12-month cohort study
- The causal role of endocrine disrupting chemicals in pubertal timing: a Mendelian randomization study
- Case Reports
- Vitamin D dependent rickets type 2A: a case series of two siblings with novel mutation in vitamin D receptor gene responded to high dose oral calcium and calcitriol
- Emergence of osteolysis as a new radiological feature in a case with a novel BMP2 gene variant
- Rare case of ACTH-independent Cushing syndrome: diagnostic challenges and management
