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11.08.2016 | Original Article | Ausgabe 12/2016

Osteoporosis International 12/2016

DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum

Zeitschrift:
Osteoporosis International > Ausgabe 12/2016
Autoren:
G. Bardai, P. Moffatt, F. H. Glorieux, F. Rauch
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s00198-016-3709-1) contains supplementary material, which is available to authorized users.

Abstract

Summary

We detected disease-causing mutations in 585 of 598 individuals (98 %) with typical features of osteogenesis imperfecta (OI). In mild OI, only collagen type I encoding genes were involved. In moderate to severe OI, mutations in 12 different genes were found; 11 % of these patients had mutations in recessive genes.

Introduction

OI is usually caused by mutations in COL1A1 or COL1A2, the genes encoding collagen type I alpha chains, but mutations in at least 16 other genes have also been associated with OI. It is presently unknown what proportion of individuals with clinical features of OI has a disease-causing mutation in one of these genes.

Methods

DNA sequence analysis was performed on 598 individuals from 487 families who had a typical OI phenotype. OI type I was diagnosed in 43 % of individuals, and 57 % had moderate to severe OI, defined as OI types other than type I.

Results

Disease-causing variants were detected in 97 % of individuals with OI type I and in 99 % of patients with moderate to severe OI. All mutations found in OI type I were dominant and exclusively affected COL1A1 or COL1A2. In moderate to severe OI, dominant mutations were found in COL1A1/COL1A2 (77 %), IFITM5 (9 %), and P4HB (0.6 %). Mutations in one of the recessive OI-associated gene were observed in 12 % of individuals with moderate to severe OI. The genes most frequently involved in recessive OI were SERPINF1 (4.0 % of individuals with moderate to severe OI) and CRTAP (2.9 %).

Conclusions

DNA sequence analysis of currently known OI-associated genes identifies disease-causing variants in almost all individuals with a typical OI phenotype. About 20 % of individuals with moderate to severe OI had mutations in genes other than COL1A1/COL1A2.

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Zusatzmaterial
ESM 1 (DOCX 239 kb)
198_2016_3709_MOESM1_ESM.docx
Literatur
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