Book ChapterDOI
Haploinsufficiency for Mutations in Type I Collagen Genes: Mechanisms and Clinical Effects
Peter H. Byers
- pp 125-127
TLDR
The most common mutation that results in dominant forms of osteogenesis imperfecta (OI) is haploinsufficiency as mentioned in this paper, which describes a state in which the protein products of one allele of a gene are not available for use.Abstract:
The most common class of mutation that results in dominant forms of osteogenesis imperfecta (OI) is haploinsufficiency. Haploinsufficiency describes a state in which the protein products of one allele of a gene are not available for use. The most common mechanism is the introduction of a premature termination codon that results in mRNA instability and loss of ability to produce protein. The most common mechanisms by which these changes occur are as a consequence of nonsense mutation, frameshifts and splice site mutation that lead to frameshifts. Virtually all these mutations occur in COL1A1 and lead to OI type I. The same class of mutations is very rare in COL1A2, probably because they do not bring the individual to clinical attention.read more
Citations
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Journal ArticleDOI
Osteogenesis imperfecta and therapeutics.
TL;DR: This short review will describe the clinical features and the molecular genetics of the disease, but then focus on how OI dysregulates all aspects of extracellular matrix biology.
Journal ArticleDOI
Genetic analysis in Japanese patients with osteogenesis imperfecta: Genotype and phenotype spectra in 96 probands
Yousuke Higuchi,Kosei Hasegawa,Natsuko Futagawa,Miho Yamashita,Hiroyuki Tanaka,Hirokazu Tsukahara +5 more
TL;DR: In this article, the genotype-phenotype correlations of COL1A1/2 and IFITM5 variants were investigated in Japanese OI patients by Sanger sequencing.
References
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Journal ArticleDOI
Osteogenesis imperfecta: cloning of a pro-alpha 2(I) collagen gene with a frameshift mutation.
TL;DR: The mutation identified in this OI patient directly demonstrates the critical role of the carboxyl-propeptides in chain selection and assembly during the biosynthesis of procollagen.
Journal Article
Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a dominant mutation in a human type I collagen gene (COL1A1).
TL;DR: Two infants with perinatal lethal osteogenesis imperfecta in one family had the same new dominant point mutation, and the observation that the mosaic individual is clinically normal suggests that genetic diseases can have both qualitative and quantitative components.
Journal ArticleDOI
Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway.
Ulrike Schwarze,Ryu-Ichiro Hata,Victor A. McKusick,Hiroshi Shinkai,H. Eugene Hoyme,Reed E. Pyeritz,Peter H. Byers +6 more
TL;DR: Computer-generated folding of a short stretch of mRNA surrounding the mutation site demonstrated realignment of the relationships between the donor and acceptor sites that could facilitate use of a cryptic donor site, suggesting that folding of the nascent mRNA could be one element that contributes to determination of order of splicing.
Journal ArticleDOI
Temporal and spatial characterization of nonsense-mediated mRNA decay
TL;DR: A spatial and temporal model for the biphasic decay of NMD targets is provided and it is determined that decay of the majority of PTC-containing β-globin mRNA occurs soon after its export into the cytoplasm, with a half-life of <1 min; the remainder is degraded with aHalflife of >12 h, similar to the half- life of normal P TC-free β- globin mRNA, indicating that it had evaded NMD.
Journal ArticleDOI
Mutation and polymorphism spectrum in osteogenesis imperfecta type II: implications for genotype–phenotype relationships
Dale L. Bodian,Ting-Fung Chan,Annie Poon,Ulrike Schwarze,Kathleen Yang,Peter H. Byers,Pui-Yan Kwok,Teri E. Klein +7 more
TL;DR: The results contribute to the understanding of the etiology of OI by providing data to evaluate and refine current models relating genotype to phenotype and by providing an unbiased indication of the relative frequency of mutations in OI-associated genes.