| Title: |
Potential therapeutic response in a severe case of autosomal dominant osteopetrosis type I |
| Authors: |
Jafri, Syed Maisam; Burke, Elizabeth A.; Adams, David R.; Evans, Colleen; Bulas, Dorothy; Weinerman, Stuart A.; Pan, Kristen; Collins, Michael T.; Markello, Thomas C.; Vezina, Gilbert; Gahl, William A.; Toro, Camilo |
| Contributors: |
National Human Genome Research Institute; National Institutse of Dental and Craniofacial Research; National Institutes of Health |
| Source: |
Journal of Translational Genetics and Genomics ; volume 6, page 281-289 ; ISSN 2578-5281 |
| Publisher Information: |
OAE Publishing Inc. |
| Publication Year: |
2022 |
| Description: |
The low-density lipoprotein receptor-related protein 5 gene (LRP5), which encodes a coreceptor within the canonical Wnt signaling pathway, plays a crucial role in bone mass regulation and has been associated with several bone disorders. Autosomal dominant osteopetrosis type I (ADO type I, OMIM 607634) is a rare disease caused by heterozygous, gain-of-function mutations in LRP5. Here we describe a 44-year-old female who presented with thickened calvarium, elevated bone density, torus palatinus, mandibular exostoses, enlarged mandible, and disabling headaches and bone pain. Exome sequencing revealed a previously reported heterozygous missense variant in the LRP5 gene (p.A242T). Post-diagnosis cranial vault volume measurement by computed tomography 3D reconstruction demonstrated decreasing intracranial volume over time. Off-label use of leuprolide acetate was associated with apparent stabilization of skull mineralization. This report documents a severe example of ADO type I and provides anecdotal evidence of the utility of therapy in need of formal evaluation. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| DOI: |
10.20517/jtgg.2021.63 |
| Availability: |
https://doi.org/10.20517/jtgg.2021.63 |
| Accession Number: |
edsbas.4F2DF046 |
| Database: |
BASE |