| Osteogenesis imperfecta (OI) is a systemic hereditary connective tissue disease, which is divided into 7 types according to clinical manifestations and signs. A research shows that over 90% of patients exhibit OI type.â… collagen gene (COL1A1 and COL1A2) change, especially in the COL1A1 gene. The relationship between its genotype and phenotype keep uncertain yet, but the molecular genetic studies show that OI clinical manifestations are relative to gene mutations certainly, and some differences exist between ethnics or families, owning its features with private mutations frequently; the research on OI gene levels has become a hot topic at home and abroad. So far in abroad, more than a thousand species of type I collagen gene mutations lead to OI have been reported, but our research still stay at a low level, such as clinical or imaging reports et al.There is lack of the research on gene mutation.ObjectiveTo find gene mutation sites, determine genetic pattern and diagnose indefinitely by clinical physical examination, family and genetic testing,4 OI proband families will be selected in this research. We will explore the relationship between OI genotype and phenotype, enrich Chinese population data in this regard, and provide a theoretical basis for its diagnosis, prevention, genetic counseling and futuristic gene therapy.MethodsThe four out-OI proband from Henan Province who were seen the Third Affiliated Hospital of Zhengzhou University from June 2008 to September 2009 were selected in this research. Their family members and some members were given some clinical health examination, some clinical data such as medical history and family surveys were collected, genetic maps of different pedigrees were drawn, genetic methods were determined, individual type and clinical diagnosis were established according to sillence classic classification proposed standards; Then by the patient and the family agreed, and approved by the hospital ethics committee, affected family members and some healthy members of the peripheral blood were taken, genomic DNA of white blood cells were extracted, PCR amplification method of application of the four proband all those who COLlA1/COL1A2 promoter, exon and exon-intron region gene amplification and gene mutation, and then the DNA sequencing were applied for four cases of proband type I collagen gene (COL1A1/COL1A2) of the fragments were sequenced to find the gene mutation, and bioinformatics software on the sequencing results were compared with the Genbank standard sequence analysis, the last four probands according to genetic test results, COL1A1/COL1A2 gene mutation of all the members were detected, sequenced, and analyzed by bioinformatics software.Results(1)Typing results of clinical diagnosis:Proband was diagnosed as typeâ…£OI, his mother typeâ… OI; proband 2 typeâ… OI; proband 3 and his father, aunt Typeâ… OI; the proband 4 and his mother typeâ… OI.(2) Genetic testing and sequencing:A c.2473 G>A mutation was found in the 36th exon of COL1A1 gene of the first propositus and the OI patients of the family, c.1821+1 G>A was found at the shearing site of the 26th intron of COL1A1 gene in the second propositus and c.697+2 C>T was found in the forth propositus at the ninth intron,then any COL1A1 or COL1A2 gene mutation was not found in the third propositus and the others.Conclusions(1)The genetic mutation of COL1A1 can lead to osteogenesis imperfecta, The genetic mutation of COL1A1 is one of the Chinese OI etiologic causes;(2) For the Chinese people, there may be existence of other genetic changes can cause osteogenesis imperfecta,in addition to COL1A1/COL1A2 gene changes;(3)The clinical manifestation is not only related with such gene changes and 01 genotype,but also with the genetic background,environment and others. |
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