Bone health in SATB2-associated syndrome: Results from a large prospective cohort and recommendations for surveillance.
SATB2
bone density
bone turnover
peripheral quantitative computed tomography
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
02 Oct 2023
02 Oct 2023
Historique:
revised:
06
09
2023
received:
24
08
2023
accepted:
08
09
2023
medline:
3
10
2023
pubmed:
3
10
2023
entrez:
3
10
2023
Statut:
aheadofprint
Résumé
Alterations in SATB2 result in SATB2-associated syndrome (SAS; Glass syndrome, OMIM 612313), an autosomal dominant multisystemic disorder predominantly characterized by developmental delay, craniofacial anomalies, and growth retardation. The bone phenotype of SAS has been less explored until recently and includes a variety of skeletal deformities, increased risk of low bone mineral density (BMD) with a propensity to fractures, and other biochemical abnormalities that suggest elevated bone turnover. We present the results of ongoing surveillance of bone health from 32 individuals (47% females, 3-18 years) with molecularly-confirmed SAS evaluated at a multidisciplinary clinic. Five individuals (5/32, 16%) were documented to have BMD Z-scores by DXA scans of -2.0 SD or lower and 7 more (7/32, 22%) had Z-scores between -1 and - 2 SD at the lumbar spine or the total hip. Alkaline phosphatase levels were found to be elevated in 19 individuals (19/30, 63%) and determined to correspond to bone-specific alkaline phosphatase elevations when measured (11/11, 100%). C-telopeptide levels were found to be elevated when adjusted by age and gender in 6 individuals (6/14, 43%). Additionally, the two individuals who underwent bone cross-sectional geometry evaluation by peripheral quantitative computed tomography were documented to have low cortical bone density for age and sex despite concurrent DXA scans that did not have this level of decreased density. While we could not identify particular biochemical abnormalities that predicted low BMD, the frequent elevations in markers of bone formation and resorption further confirmed the increased bone turnover in SAS. Based on our results and other recently published studies, we propose surveillance guidelines for the skeletal phenotype of SAS.
Identifiants
pubmed: 37786328
doi: 10.1002/ajmg.a.63421
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : SATB2 Gene Foundation
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Bengani, H., Handley, M., Alvi, M., Ibitoye, R., Lees, M., Lynch, S. A., Lam, W., Fannemel, M., Nordgren, A., Malmgren, H., Kvarnung, M., Mehta, S., McKee, S., Whiteford, M., Stewart, F., Connell, F., Clayton-Smith, J., Mansour, S., Mohammed, S., … FitzPatrick, D. R. (2017). Clinical and molecular consequences of disease-associated de novo mutations in SATB2. Genetics in Medicine, 19(8), 900-908.
Boone, P. M., Chan, Y. M., Hunter, J. V., Pottkotter, L. E., Davino, N. A., Yang, Y., Beuten, J., & Bacino, C. A. (2016). Increased bone turnover, osteoporosis, progressive tibial bowing, fractures, and scoliosis in a patient with a final-exon SATB2 frameshift mutation. American Journal of Medical Genetics Part A, 170(11), 3028-3032.
Britanova, O., Depew, M. J., Schwark, M., Thomas, B. L., Miletich, I., Sharpe, P., & Tarabykin, V. (2006). Satb2 haploinsufficiency phenocopies 2q32-q33 deletions, whereas loss suggests a fundamental role in the coordination of jaw development. American Journal of Human Genetics, 79(4), 668-678.
Chen, J. R., Zhao, H., Lazarenko, O. P., Blackburn, M. L., & Shankar, K. (2020). Maternal regulation of SATB2 in osteo-progeniters impairs skeletal development in offspring. The FASEB Journal, 34(2), 2511-2523.
Dobreva, G., Chahrour, M., Dautzenberg, M., Chirivella, L., Kanzler, B., Farinas, I., Karsenty, G., & Grosschedl, R. (2006). SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation. Cell, 125(5), 971-986.
Dowrey, T., Schwager, E. E., Duong, J., Merkuri, F., Zarate, Y. A., & Fish, J. L. (2019). Satb2 regulates proliferation and nuclear integrity of pre-osteoblasts. Bone, 127, 488-498.
Fish, J. L., Villmoare, B., Kobernick, K., Compagnucci, C., Britanova, O., Tarabykin, V., & Depew, M. J. (2011). Satb2, modularity, and the evolvability of the vertebrate jaw. Evolution & Development, 13(6), 549-564.
Lo, H. Y., Ng, W. F., Fong, N. C., Lui, C. D., & Lam, C. W. (2022). Novel finding of lissencephaly and severe osteopenia in a Chinese patient with SATB2-associated syndrome and a brief review of literature. American Journal of Medical Genetics Part A, 188(7), 2168-2172.
Mouille, M., Rio, M., Breton, S., Piketty, M. L., Afenjar, A., Amiel, J., Capri, Y., Goldenberg, A., Francannet, C., Michot, C., Mignot, C., Perrin, L., Quelin, C., Van Gils, J., Barcia, G., Pingault, V., Maruani, G., Koumakis, E., & Cormier-Daire, V. (2022). SATB2-associated syndrome: Characterization of skeletal features and of bone fragility in a prospective cohort of 19 patients. Orphanet Journal of Rare Diseases, 17(1), 100.
Ye, J. H., Xu, Y. J., Gao, J., Yan, S. G., Zhao, J., Tu, Q., Zhang, J., Duan, X. J., Sommer, C. A., Mostoslavsky, G., Kaplan, D. L., Wu, Y. N., Zhang, C. P., Wang, L., & Chen, J. (2011). Critical-size calvarial bone defects healing in a mouse model with silk scaffolds and SATB2-modified iPSCs. Biomaterials, 32(22), 5065-5076.
Zarate, Y. A., Bosanko, K. A., Caffrey, A. R., Bernstein, J. A., Martin, D. M., Williams, M. S., Berry-Kravis, E. M., Mark, P. R., Manning, M. A., Bhambhani, V., Vargas, M., Seeley, A. H., Estrada-Veras, J. I., van Dooren, M. F., Schwab, M., Vanderver, A., Melis, D., Alsadah, A., Sadler, L., … Fish, J. L. (2019). Mutation update for the SATB2 gene. Human Mutation, 40(8), 1013-1029.
Zarate, Y. A., & Fish, J. L. (2016). SATB2-associated syndrome: Mechanisms, phenotype, and practical recommendations. American Journal of Medical Genetics Part A, 173, 327-337.
Zarate, Y. A., Kaylor, J., & Fish, J. (1993). SATB2-associated syndrome. In M. P. Adam, H. H. Ardinger, R. A. Pagon, S. E. Wallace, L. J. H. Bean, H. C. Mefford, K. Stephens, A. Amemiya, & N. Ledbetter (Eds.), GeneReviews(R). https://www.ncbi.nlm.nih.gov/books/NBK1116/
Zarate, Y. A., Steinraths, M., Matthews, A., Smith, W. E., Sun, A., Wilson, L. C., Brain, C., Allgove, J., Jacobs, B., Fish, J. L., Powell, C. M., Wasserman, W. W., van Karnebeek, C. D., Wakeling, E. L., & Ma, N. S. (2018). Bone health and SATB2-associated syndrome. Clinical Genetics, 93(3), 588-594.
Zhang, J., Tu, Q., Grosschedl, R., Kim, M. S., Griffin, T., Drissi, H., Yang, P., & Chen, J. (2011). Roles of SATB2 in osteogenic differentiation and bone regeneration. Tissue Engineering. Part A, 17(13-14), 1767-1776.