A novel compound heterozygous variation in the FKBP10 gene causes Bruck syndrome without congenital contractures: A case report
Liyuan Shang,
Weizhe Shi,
Yibo Xu,
Tianying Nong,
Xia Li,
Zhaohui Li,
Yanhan Liu,
Jingchun Li,
Ya-Ping Tang,
Mingwei Zhu,
Hongwen Xu
Affiliations
Liyuan Shang
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Weizhe Shi
Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Yibo Xu
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Tianying Nong
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Xia Li
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Zhaohui Li
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Yanhan Liu
Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Jingchun Li
Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Ya-Ping Tang
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Corresponding author.
Mingwei Zhu
Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Corresponding author. Guangzhou Women and Children's Medical Center, 9 Jinsui Road, Guangzhou, Guangdong Province, 510623, China.
Hongwen Xu
Department of Pediatric Orthopedics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China; Corresponding author.
Background: Bruck syndrome (BS) is an extremely rare autosomal-recessive connective tissue disorder mainly characterized by bone fragility, congenital joint contracture, and spinal deformity. It is also considered as a rare form of osteogenesis imperfecta (OI) due to features of osteopenia and fragility fractures. Its two forms, BS1 and BS2, are caused by pathogenic variations in FKBP10 and PLOD2, respectively. Objective: We aimed to improve the clinical understanding of BS by presenting a case from China and to identify the genetic variants that led to this case. Methods: OI was suspected in a Chinese boy with a history of recurrent long bone fractures, lumbar kyphosis, and dentinogenesis imperfecta (DI). Whole-exome sequencing (WES) was performed to identify pathogenic variations. Sanger sequencing was used to confirm the results of the WES. In silico analysis was used to predict the pathogenicity of genetic variants. Results: WES and Sanger sequencing revealed a compound heterozygous variation in the FKBP10 gene (NM_021939, c.23dupG in exon 1, and c.825dupC in exon 5). Both variants resulted in a frameshift and premature stop codon. Of these two variants, c.23dupG has not been previously reported. The patient's parents were heterozygous carriers of one variant. In addition, zoledronic acid treatment improved the vertebral deformity and bone mineral density (BMD) significantly in this patient. Conclusions: A novel compound heterozygous variation of FKBP10, c.23dupG/c.825dupC, was identified in a patient with moderately severe OI. Based on these findings, the patient was diagnosed with BS1 without congenital joint contractures or OI type XI. This study expands the spectrum of FKBP10 genetic variants that cause BS and OI.
