The Study Of Clinical Manifestations And Genetic Characteristics Of Osteogenesis Imperfecta In A Chinese Family

Osteogenesis imperfecta (OI) is a genetic disease of connective tissue, also known as brittle bone disease ,which is a single-gene genetic disorder characterized by typical manifestations including bone fragility, bone deformities, blue sclera, hearing impairment and dentinogenesis imperfecta. The prevalence rate of OI is 1/10000-30000 in Europe and no relevant data were reported in China. The most mode of inheritance is autosomal dominant inheritance, rarely being autosomal recessive disorder. Usually more than one member was involved in a family. OI was divided into seven subtypes clinically. The diversities of manifestations were found in patients with OI. An OI family was found and their clinical manifestations, family tree, gene mutation and outcome of treatment were studied.Objective: To study the clinical characters, the mode of inheritance and gene mutation as well as to investigate the molecular pathogenesis and molecular biology diagnostic methods of OI family.Methods: Clinical data and blood samples of proband and their family members were collected. The family patterns were mapped. clinical features were summarized and analyzed. Genome DNA was obtained from peripheral blood. PCR was performed for all of exons and exon-intron boundaries of COL1A1 and COL1A2, and products were sequenced. Sequencing results were compared with Gene Bank database and confirmed through cloning (TA cloning) sequencing.PCR and sequencing were also checked with the same methods in other family members.Results:1. Clinical features: There are sixty members of four generations in the family. 20 cases including proband's mother and cousin were diagnosed as having OI type I based on clinical manifestations. 15 cases of blue sclera, 16 cases of dentinogenesis imperfecta, 5 cases of hearing loss and 3 cases of fracture were found. Thyroid cancer and Turner syndrome were also found in proband's mother and cousin respectively. The genetic map showed that the disease was autosomal dominant inheritance.2. Genetic abnormality: 700delG loss of heterozygosity G at the 10th exon of COL1A1 gene were found in Proband and her mother. Other members were not found gene mutation. The gene mutation in COL1A2 were not found in proband.3. Treatment: The proband, her mother and her cousin were treated with alendronate for two years. Bone pain relieved and bone mineral density increased significantly, and no fracture occurred so far.Conclusion:1. This OI family was diagnosed as having OI type I. The mode of inheritance is autosomal dominant inheritance.2. 700delG loss of heterozygosity G at the 10th exon of COL1A1 gene were found. This mutation was not reported yet.3. Bisphosphonates may be an effective drug for treatment of OI...