A novel mutation in PLS3 causes extremely rare X-linked osteogenesis imperfecta
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Updated: Dec 1, 2025
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Jing Hu1, Lu-Jiao Li1,2, Wen-Bin Zheng1
1Department of Endocrinology, National Health Commission Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Background:
Osteogenesis imperfecta (OI) is a phenotypically and genetically heterogeneous bone disease characterized by bone fragility and recurrent fractures. X-linked inherited OI with mutation in PLS3 is so rare that its genotype-phenotype characteristics are not available.
Methods:
We designed a novel targeted next-generation sequencing (NGS) panel with the candidate genes of OI to detect pathogenic mutations and confirmed them by Sanger sequencing. The phenotypes of the patients were also investigated.
Results:
The proband, a 12-year-old boy from a nonconsanguineous family, experienced multiple fractures of long bones and vertebrae and had low bone mineral density (BMD Z-score of -3.2 to -2.0). His younger brother also had extremity fractures. A novel frameshift mutation (c.1106_1107insGAAA; p.Phe369Leufs*5) in exon 10 of PLS3 was identified in the two patients, which was inherited from their mother who had normal BMD. Blue sclerae were the only extraskeletal symptom in all affected individuals. Zoledronic acid was beneficial for increasing BMD and reshaping the compressed vertebral bodies of the proband.
Conclusion:
We first identify a novel mutation in PLS3 that led to rare X-linked OI and provide practical information for the diagnosis and treatment of this disease.
Insights
This study identifies a new PLS3 gene mutation causing rare X-linked osteogenesis imperfecta (OI). The findings offer crucial insights for diagnosing and treating this brittle bone disease.
Area of Science:
- Genetics
- Molecular Biology
- Pediatrics
Background:
- Osteogenesis imperfecta (OI) is a group of genetic disorders characterized by bone fragility.
- X-linked OI caused by PLS3 mutations is exceptionally rare, with limited genotype-phenotype data.
- Understanding rare genetic variants is crucial for diagnosing and managing inherited bone diseases.
Observation:
- A novel frameshift mutation (c.1106_1107insGAAA; p.Phe369Leufs*5) in the PLS3 gene was identified in two brothers with OI.
- The mutation was maternally inherited, though the mother exhibited normal bone mineral density.
- Affected individuals presented with bone fractures, low bone mineral density, and blue sclerae.
Findings:
- Next-generation sequencing (NGS) and Sanger sequencing confirmed the novel PLS3 mutation in patients.
- The identified mutation provides a new genetic cause for X-linked osteogenesis imperfecta.
- Zoledronic acid treatment improved bone mineral density and vertebral bone structure in the proband.
Implications:
- This research expands the known genetic spectrum of osteogenesis imperfecta.
- Early diagnosis and targeted treatment can improve outcomes for patients with rare OI.
- Further research into PLS3 mutations will enhance understanding of X-linked OI pathogenesis.
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