Genetic Causes and Mechanisms of Osteogenesis Imperfecta

Overview

Journal Bone

Specialties Endocrinology
Orthopedics

Date 2017 Feb 25

PMID 28232077

Citations 45

Authors

Joohyun Lim

Ingo Grafe

Stefanie Alexander

Brendan Lee

Affiliations

Soon will be listed here.

Abstract

Osteogenesis Imperfecta (OI) is a genetic disorder characterized by various clinical features including bone deformities, low bone mass, brittle bones, and connective tissue manifestations. The predominant cause of OI is due to mutations in the two genes that encode type I collagen. However, recent advances in sequencing technology has led to the discovery of novel genes that are implicated in recessive and dominant OI. These include genes that regulate the post-translational modification, secretion and processing of type I collagen as well as those required for osteoblast differentiation and bone mineralization. As such, OI has become a spectrum of genetic disorders informing about the determinants of both bone quantity and quality. Here we summarize the known genetic causes of OI, animal models that recapitulate the human disease and mechanisms that underlie disease pathogenesis. Additionally, we discuss the effects of disrupted collagen networks on extracellular matrix signaling and its impact on disease progression.

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