Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I: identification of common sequences of null-allele mutations.
Currently, heterozygous Mov-13 mice generated by virus insertion in the first intron of col1a1 is the exclusive model to modulate OI type I, in spite of the gradually recovered bone mineral and mechanical properties.
Generation of a patient-specific induced pluripotent stem cell line, KSCBi006-A, for osteogenesis imperfecta type I with the COL1A1, c.3162delT mutation.
The aim of this study is to find mutational patterns of COL1A1 gene that may account for the putative Van der Hoeve syndrome in the patients carrying symptoms of osteogenesis imperfecta, blue sclera, and conductive deafness.
Our data suggest that nonsense and frameshift mutations throughout most of the COL1A1 gene result in a null allele, which is associated with the predictable mild clinical phenotype, OI type 1.
Some phenotype correlations, notably between the OI type IV phenotype and linkage to COL1A2 and between presenile hearing loss in OI type I and linkage to COL1A1, can be used to improve risk estimates substantially in families where there are no segregation data to distinguish whether COL1A1 or COL1A2 is the mutant locus.
These results suggest that mutations in COL1A1 that are similar to those that occur in type I osteogenesis imperfecta may account for a small percentage of cases of otosclerosis, and that the majority of cases of clinical otosclerosis are related to other genetic abnormalities that have yet to be identified.
Phenotypes correlate with the mutation types in that COL1A1 null mutations lead to OI type I, and structural mutations in alpha1(I) or alpha2(I) lead to more severe OI types (II-IV).
The missense mutation c.3235G>A was identified within exon 45 of the COL1A1 gene in a 16-year-old girl diagnosed as having OI type I; it resulted in substitution of a glycine residue (G) by a serine (S) at codon 1079 (p.G1079S).
To determine the frequency of such mutations in OI type I cell strains, we used PCR amplified genomic DNA in conjunction with denaturing gradient gel electrophoresis (DGGE) and SSCP, to screen the 5' untranslated domain, exon 1, and a small portion of intron 1 of the COL1A1 gene.
As such, multiplex ligation-dependent probe amplification analysis of the COL1A1 gene is a useful additional approach to defining the mutation in cases of suspected osteogenesis imperfecta type I with no detectable mutation.