Novel compound heterozygous mutations in SERPINH1 cause rare autosomal recessive osteogenesis imperfecta type X.

Abstract

We identified novel compound heterozygous mutations in SERPINH1 in a Chinese boy suffering from recurrent fractures, femoral deformities, and growth retardation, which resulted in extremely rare autosomal recessive OI type X. Long-term treatment of BPs was effective in increasing BMD Z-score, reducing fracture incidence and reshaping vertebrae compression.

INTRODUCTION:

Osteogenesis imperfecta (OI) is a heritable bone disorder characterized by low bone mineral density, recurrent fractures, and progressive bone deformities. Mutation in serpin peptidase inhibitor clade H, member 1 (SERPINH1), which encodes heat shock protein 47 (HSP47), leads to rare autosomal recessive OI type X. We aimed to detect the phenotype and the pathogenic mutation of OI type X in a boy from a non-consanguineous Chinese family.

METHODS:

We investigated the pathogenic mutations and analyzed their relationship with the phenotype in the patient using next-generation sequencing (NGS) and Sanger sequencing. Moreover, the efficacy of long-term bisphosphonate treatment in this patient was evaluated.

RESULTS:

The patient suffered from multiple fractures, low bone mass, and bone deformities in the femur, without dentinogenesis imperfecta or hearing loss. Compound heterozygous variants were found in SERPINH1 as follows: c.149 T>G in exon 2 and c.1214G>A in exon 5. His parents were heterozygous carriers of each of these mutations, respectively. Bisphosphonates could be helpful in increasing BMD Z-score, reducing bone fracture risk and reshaping the compressed vertebral bodies of this patient.

CONCLUSION:

We reported novel compound heterozygous mutations in SERPINH1 in a Chinese OI patient for the first time, which expanded the spectrum of phenotype and genotype of extremely rare OI type X.

• Authors: Y Song, D Zhao, X Xu, F Lv, L Li, Y Jiang, O Wang, W Xia, X Xing, M Li
• Journal: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA (Osteoporos Int) Vol. 29 Issue 6 Pg. 1389-1396 (Jun 2018) ISSN: 1433-2965 [Electronic] England
• PMID: 29520608 (Publication Type: Case Reports, Journal Article)

Chemical References

• Bone Density Conservation Agents
• Diphosphonates
• HSP47 Heat-Shock Proteins
• SERPINH1 protein, human

Topics

• Bone Density Conservation Agents (therapeutic use)
• Child, Preschool
• Diphosphonates (therapeutic use)
• Follow-Up Studies
• HSP47 Heat-Shock Proteins (genetics)
• Heterozygote
• High-Throughput Nucleotide Sequencing
• Humans
• Male
• Mutation
• Osteogenesis Imperfecta (complications, diagnostic imaging, drug therapy, genetics)
• Osteoporotic Fractures (etiology, genetics, prevention & control)
• Phenotype
• Radiography