Osteogenesis imperfecta: clinical, biochemical and molecular findings

Venturi, Giacomo; Tedeschi, Elisa; Mottes, Monica; Valli, Maurizia; Camilot, Marta; Viglio, Simona; Antoniazzi, Franco; Tatò, Luciano

doi:10.1111/j.1399-0004.2006.00646.x

Cited by 48 publications

(37 citation statements)

References 33 publications

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“…COL1A1 is 18 kb in size and is located at 17q21.3-q22. COL1A2 is 38 kb and is located at 7q21.3-q22.1 (Vuorio and de Crombrugghe, 1990;Venturi et al, 2006). The two genes are similar in structure: COL1A1 and COL1A2 have 51 and 52 exons, respectively.…”

Section: Discussionmentioning

confidence: 99%

Mutation characteristics in type I collagen genes in Chinese patients with osteogenesis imperfecta

Zhong

Ke²,

Zeng³

et al. 2011

Genet. Mol. Res.

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ABSTRACT. Osteogenesis imperfecta is normally caused by an autosomal dominant mutation in the type I collagen genes COL1A1 and COL1A2. The severity of osteogenesis imperfecta varies, ranging from perinatal lethality to a very mild phenotype. Although there have been many reports of COL1A1 and COL1A2 mutations, few cases have been reported in Chinese people. We report on five unrelated families and three sporadic cases. The mutations were detected by PCR and direct sequencing. Four mutations in COL1A1 and one in COL1A2 were found, among which three mutations were previously unreported. The mutation rates of G>C at base 128 in intron 31 of the COL1A1 gene and G>A at base 162 in intron 30 of the COL1A2 gene were higher than normal. The patients' clinical characteristics with the same mutation were variable even in the same family. We conclude that mutations in COL1A1 and COL1A2 also have an important role in osteogenesis imperfecta in the Chinese population. As the Han Chinese people account for a quarter of the world's population, these new data contribute to the type I collagen mutation map.

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Section: Discussionmentioning

confidence: 99%

Mutation characteristics in type I collagen genes in Chinese patients with osteogenesis imperfecta

Zhong

Ke²,

Zeng³

et al. 2011

Genet. Mol. Res.

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“…Various investigators have reported on the dental status of OI patients with glycine mutations in this region of the collagen type I triple helix and none of the nine patients mentioned in these reports had clear clinical evidence of dentinogenesis imperfecta. [14][15][16][17][18] The mechanistic link between collagen type I mutations and dentinogenesis imperfecta has not been elucidated in any detail. Our data nevertheless show that patients sharing the same mutation had a high concordance for the condition.…”

Section: Resultsmentioning

confidence: 99%

Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I

et al. 2010

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Osteogenesis imperfecta (OI) is a heritable disorder with bone fragility that is often associated with short stature, tooth abnormalities (dentinogenesis imperfecta), and blue sclera. The most common mutations associated with OI result from the substitution for glycine by another amino acid in the triple helical domain of either the a1 or the a2 chain of collagen type I. In this study, we compared the results of genotype analysis and clinical examination in 161 OI patients (median age: 13 years) who had glycine mutations in the triple helical domain of a1(I) (n¼67) or a2(I) (n¼94). Serine substitutions were the most frequently encountered type of mutation in both chains. Compared with patients with serine substitutions in a2(I) (n¼40), patients with serine substitutions in a1(I) (n¼42) on average were shorter (median height z-score À6.0 vs À3.4; P¼0.005), indicating that a1(I) mutations cause a more severe phenotype. Height correlated with the location of the mutation in the a2(I) chain but not in the a1(I) chain. Patients with mutations affecting the first 120 amino acids at the amino-terminal end of the collagen type I triple helix had blue sclera but did not have dentinogenesis imperfecta. Among patients from different families sharing the same mutation, about 90 and 75% were concordant for dentinogenesis imperfecta and blue sclera, respectively. These data should be useful to predict disease phenotype in newly diagnosed OI patients.

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“…type II. Most OI cases are caused by heterozygosity of dominant mutations in one of the two genes encoding the chains of type I collagen (COL1A1 and COL1A2) (3), with quantitative (-qt; mild or moderate forms) or qualitative (-ql; severe or lethal forms) defects of the synthesis of type I collagen (4). Cartilage-associated protein (CRTAP), prolyl 3-hydroxylase 1 (P3H1/LEPRE1), and cyclophilin B (CyPB/PPIB) form an intracellular collagen-modifying complex that 3-hydroxylates proline at position 986 (P986) in the a1 chains of collagen (types I, II, and V); mutations in these essential cofactors cause alterations in the posttranslational chain modification and collagen folding, which are responsible for autosomal-recessive lethal or severe OI (5)(6)(7)(8)(9)(10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

GH in combination with bisphosphonate treatment in osteogenesis imperfecta

Antoniazzi

Monti²,

Venturi³

et al. 2010

European Journal of Endocrinology

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Objective: To verify the effects of bisphosphonates (Bps) in combination with recombinant human GH (rGH) in pediatric osteogenesis imperfecta (OI) patients; we focused on possible improvement of bone mineral density (BMD), projected bone areas, growth velocity, and fractures risk. Design: A randomized controlled 1-year clinical trial on 30 prepubertal children (M:FZ14:16) affected by OI (type I, IV, and III) being treated with neridronate. Methods: Following an observational period of 12 months during ongoing neridronate treatment, the patients were randomly divided into two groups: 15 were treated for 12 months with rGH and neridronate (group BpCrGH) and 15 continued neridronate alone (group Bp). We evaluated auxological parameters, number of fractures, bone age (BA), bone metabolic parameters, and bone mass measurements (at lumbar spine and radius by dual-energy X-ray absorptiometry). Results: The mean variation in percentage of BMD (D%BMD) -at lumbar spine (L2-L4), at distal and ultradistal radius -and the projected area of lumbar spine increased significantly in group BpCrGH (P!0.05). Growth velocity was significantly higher during rGH treatment in group BpCrGH versus group Bp and versus pretreatment (P!0.05), with no difference in increase in BA or fracture risk rate. Patients with quantitative (-qt) collagen synthesis defects had a higher, although not significant, response to rGH in terms of growth velocity and BMD. Conclusions: In OI patients, the combined rGH-Bp treatment may give better results than Bp treatment alone, in terms of BMD, lumbar spine projected area and growth velocity, particularly in patients with quantitative defects.

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Osteogenesis imperfecta: clinical, biochemical and molecular findings

Cited by 48 publications

References 33 publications

Mutation characteristics in type I collagen genes in Chinese patients with osteogenesis imperfecta

Mutation characteristics in type I collagen genes in Chinese patients with osteogenesis imperfecta

Genotype–phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I

GH in combination with bisphosphonate treatment in osteogenesis imperfecta

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