Three novel type I collagen mutations in osteogenesis imperfecta type IV probands are associated with discrepancies between electrophoretic migration of osteoblast and fibroblast collagen

1. Skin fibroblast lines were cultured from nine patients who had the features of idiopathic juvenile osteoporosis, six relatives, five unrelated control subjects and three unrelated patients with osteogenesis imperfecta type I. Some patients with idiopathic juvenile osteoporosis were adults whose previous osteoporosis was in remission. Two patients with idiopathic juvenile osteoporosis were siblings and one patient with idiopathic juvenile osteoporosis had a daughter with severe osteogenesis imperfecta (type III). 2. The ratio of type III to type I collagen, synthesized by fibroblasts, was increased in two of the patients with osteogenesis imperfecta type I and in the daughter with osteogenesis imperfecta type III, but was normal in all the other patients with idiopathic juvenile osteoporosis and the other relatives. 3. Radiolabelled collagen was digested by cyanogen bromide and separated on SDS-PAGE. Unreduced collagen peptides migrated normally, except those from both the two siblings with idiopathic juvenile osteoporosis. In these two lines, abnormal migration suggested the presence of collagen I mutations. 4. The secretion of synthesized collagen by these two idiopathic juvenile osteoporosis lines and two others was reduced to only 43–45% as compared with a line from a 13-year-old control subject, which was defined as 100%. The three osteogenesis imperfecta type I lines secreted 18–37%, the other five idiopathic juvenile osteoporosis lines secreted 57–75%, the relatives (including the daughter with severe osteogenesis imperfecta) secreted 49–115% and the controls secreted 69–102%. 5. We conclude that qualitative abnormalities of type I collagen associated with a reduction in total secreted collagen synthesis may occur in a minority of patients with idiopathic juvenile osteoporosis; these patients could represent a subset of patients with this disorder.

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Osteogenesis imperfecta type III: mutations in the type I collagen structural genes, COL1A1 and COL1A2, are not necessarily responsible.

Journal of Medical Genetics ◽

10.1136/jmg.30.6.492 ◽

1993 ◽

Vol 30 (6) ◽

pp. 492-496 ◽

Cited By ~ 45

Author(s):

G A Wallis ◽

B Sykes ◽

P H Byers ◽

C G Mathew ◽

D Viljoen ◽

...

Keyword(s):

Osteogenesis Imperfecta ◽

Type I Collagen ◽

Type I ◽

Osteogenesis Imperfecta Type ◽

Structural Genes ◽

Type Iii

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Substitution of glycine-172 by arginine in the α1 chain of type I collagen in a patient with osteogenesis imperfecta, type III

Human Mutation ◽

10.1002/humu.1380030327 ◽

1994 ◽

Vol 3 (3) ◽

pp. 324-326 ◽

Cited By ~ 2

Author(s):

Katrina Mackay ◽

Anne De Paepe ◽

Lieve Nuytinck ◽

Raymond Dalgleish

Keyword(s):

Osteogenesis Imperfecta ◽

Type I Collagen ◽

Type I ◽

Osteogenesis Imperfecta Type ◽

Type Iii

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Osteogenesis Imperfecta: The Impact of Genotype and Clinical Phenotype on Adiposity and Resting Energy Expenditure

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab679 ◽

2021 ◽

Author(s):

Kaitlin L Ballenger ◽

Nicol Tugarinov ◽

Sara K Talvacchio ◽

Marianne M Knue ◽

An N Dang Do ◽

...

Keyword(s):

Energy Expenditure ◽

Osteogenesis Imperfecta ◽

Type I Collagen ◽

Resting Energy Expenditure ◽

Type I ◽

Healthy Controls ◽

Type Iv ◽

Reduced Mobility ◽

The Impact ◽

Resting Energy

Abstract Context Mutations in type I collagen or collagen-related proteins cause Osteogenesis Imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced mobility, or intrinsic defects in osteoblast differentiation increasing adipocyte development. Objective Compare adiposity and resting energy expenditure (REE) in OI and healthy controls (HC), for OI genotype- and Type-associated differences. Design/Setting/Participants We studied 90 participants, 30 with OI (13 COL1A1 Gly, 6 COL1A2 Gly, 3 COL1A1 non-Gly, 2 COL1A2 non-Gly, 6 non-COL; 8 Type III, 16 Type IV, 4 Type VI, 1 Type VII, 1 Type XIV) and 60 HC with sociodemographic characteristics/BMI/BMIz similar to the OI group. Participants underwent dual-energy X-ray absorptiometry to determine lean mass and fat mass percentage (FM%) and REE. FM% and REE were compared, adjusting for covariates to examine the relationship of OI genotypes and phenotypic Types. Results FM% did not differ significantly in all patients with OI versus HC (OI: 36.6±1.9%, HC: 32.7±1.2%, p =0.088). FM% was, however, greater than HC for those with non-COL variants (p=0.018). FM% did not differ from HC among OI Types (p’s>0.05). Overall, covariate-adjusted REE did not differ significantly between OI and HC (OI: 1376.5±44.7 kcal/d, healthy controls: 1377.0±96 kcal/d p=0.345). However, those with non-COL variants (p=0.034) and Type VI OI (p=0.04) had significantly lower REE than HC. Conclusions Overall, patients with OI did not significantly differ in either extra-marrow adiposity or REE from BMI-similar HC. However, reduced REE among those with non-COL variants may contribute to greater adiposity.

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