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Substitution of glycine-661 by serine in the α1(I) and α2(I) chains of type I collagen results in different clinical and biochemical phenotypes

(1996) HUMAN GENETICS. 97(3). p.324-329
Author
Organization
Abstract
We have characterised a point mutation causing the substitution of serine for glycine at position 661 of the alpha 1(I) chain of type I collagen in a child with a severe form of osteogenesis imperfecta. An identical glycine substitution in the alpha 2(I) chain was previously detected in a woman with post-menopausal osteoporosis, Two of her sons were heterozygous for the mutation and the third son was homozygous as a result of uniparental isodisomy. Biochemical profiles of the type I collagen heterotrimers were studied in each of the patients and compared with a control, Medium and cell-layer collagens were overmodified in all patients. Overmodification was obvious in the patient with the alpha 1(I) mutation but mild in the patients with the alpha 2(I) mutation, being slightly less evident in the heterozygote than in the homozygote. Investigation of the melting curves of the mutant collagen trimers in all three patients showed the same slight decrease in thermal stability and, hence, a lack of correlation with phenotypic severity, In contrast, the degree of overmodification of the collagen alpha chains was correlated with the phenotypic severity. The clinical observations in these patients illustrate the possibly predominant role of mutations in the collagen alpha 1(I) chains over the same mutations in the alpha 2(I) chains in determining the clinical outcome.
Keywords
TRIPLE HELIX, PERINATAL OSTEOGENESIS IMPERFECTA, THERMAL-STABILITY, REGIONAL MODEL, MUTATIONS, PROCOLLAGEN, GENE

Citation

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MLA
Nuytinck, Lieve, Raymond Dalgleish, Loretta Spotila, et al. “Substitution of Glycine-661 by Serine in the α1(I) and α2(I) Chains of Type I Collagen Results in Different Clinical and Biochemical Phenotypes.” HUMAN GENETICS 97.3 (1996): 324–329. Print.
APA
Nuytinck, Lieve, Dalgleish, R., Spotila, L., Renard, J.-P., Van Regemorter, N., & De Paepe, A. (1996). Substitution of glycine-661 by serine in the α1(I) and α2(I) chains of type I collagen results in different clinical and biochemical phenotypes. HUMAN GENETICS, 97(3), 324–329.
Chicago author-date
Nuytinck, Lieve, Raymond Dalgleish, Loretta Spotila, Jean-Pierre Renard, Nicole Van Regemorter, and Anne De Paepe. 1996. “Substitution of Glycine-661 by Serine in the α1(I) and α2(I) Chains of Type I Collagen Results in Different Clinical and Biochemical Phenotypes.” Human Genetics 97 (3): 324–329.
Chicago author-date (all authors)
Nuytinck, Lieve, Raymond Dalgleish, Loretta Spotila, Jean-Pierre Renard, Nicole Van Regemorter, and Anne De Paepe. 1996. “Substitution of Glycine-661 by Serine in the α1(I) and α2(I) Chains of Type I Collagen Results in Different Clinical and Biochemical Phenotypes.” Human Genetics 97 (3): 324–329.
Vancouver
1.
Nuytinck L, Dalgleish R, Spotila L, Renard J-P, Van Regemorter N, De Paepe A. Substitution of glycine-661 by serine in the α1(I) and α2(I) chains of type I collagen results in different clinical and biochemical phenotypes. HUMAN GENETICS. 1996;97(3):324–9.
IEEE
[1]
L. Nuytinck, R. Dalgleish, L. Spotila, J.-P. Renard, N. Van Regemorter, and A. De Paepe, “Substitution of glycine-661 by serine in the α1(I) and α2(I) chains of type I collagen results in different clinical and biochemical phenotypes,” HUMAN GENETICS, vol. 97, no. 3, pp. 324–329, 1996.
@article{187045,
  abstract     = {We have characterised a point mutation causing the substitution of serine for glycine at position 661 of the alpha 1(I) chain of type I collagen in a child with a severe form of osteogenesis imperfecta. An identical glycine substitution in the alpha 2(I) chain was previously detected in a woman with post-menopausal osteoporosis, Two of her sons were heterozygous for the mutation and the third son was homozygous as a result of uniparental isodisomy. Biochemical profiles of the type I collagen heterotrimers were studied in each of the patients and compared with a control, Medium and cell-layer collagens were overmodified in all patients. Overmodification was obvious in the patient with the alpha 1(I) mutation but mild in the patients with the alpha 2(I) mutation, being slightly less evident in the heterozygote than in the homozygote. Investigation of the melting curves of the mutant collagen trimers in all three patients showed the same slight decrease in thermal stability and, hence, a lack of correlation with phenotypic severity, In contrast, the degree of overmodification of the collagen alpha chains was correlated with the phenotypic severity. The clinical observations in these patients illustrate the possibly predominant role of mutations in the collagen alpha 1(I) chains over the same mutations in the alpha 2(I) chains in determining the clinical outcome.},
  author       = {Nuytinck, Lieve and Dalgleish, Raymond and Spotila, Loretta and Renard, Jean-Pierre and Van Regemorter, Nicole and De Paepe, Anne},
  issn         = {0340-6717},
  journal      = {HUMAN GENETICS},
  keywords     = {TRIPLE HELIX,PERINATAL OSTEOGENESIS IMPERFECTA,THERMAL-STABILITY,REGIONAL MODEL,MUTATIONS,PROCOLLAGEN,GENE},
  language     = {eng},
  number       = {3},
  pages        = {324--329},
  title        = {Substitution of glycine-661 by serine in the α1(I) and α2(I) chains of type I collagen results in different clinical and biochemical phenotypes},
  url          = {http://dx.doi.org/10.1007/BF02185764},
  volume       = {97},
  year         = {1996},
}

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