Congenital blindness and osteoporosis-pseudoglioma syndrome

Lee, Dave H.; Wenkert, Deborah; Whyte, Michael P.; Trese, Michael T.; Cruz, Oscar A.

doi:10.1016/s1091-8531(03)00051-x

Cited by 15 publications

(4 citation statements)

References 6 publications

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“…Loss‐of‐function LRP5 mutations cause osteoporosis pseudoglioma syndrome (OPPG; OMIM# 259770), a rare autosomal recessive disorder characterized by congenital or juvenile‐onset blindness, severe juvenile‐onset osteoporosis, skeletal fragility, and occasionally learning difficulties . Approximately 70 cases have been reported worldwide .…”

Section: Introductionmentioning

confidence: 99%

Atypical Femoral Fracture in Osteoporosis Pseudoglioma Syndrome Associated with Two Novel Compound Heterozygous Mutations in LRP5

Alonso

Soares

McCloskey

et al. 2014

Journal of Bone and Mineral Research

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Osteoporosis pseudoglioma syndrome (OPPG) is a rare autosomal recessive condition of congenital blindness and severe childhood osteoporosis with skeletal fragility, caused by loss-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. We report the first case of atypical (subtrochanteric) femoral fracture (AFF) in OPPG, occurring in a 38-year-old man within the context of relatively low bone turnover and trabecular osteoporosis on bone histology. We identify two novel LRP5 mutations: R752W is associated with low bone mineral density (BMD), as demonstrated by the heterozygous carriage identified in his 57-year-old mother; however, the combination of this R752W mutation with another novel W79R mutation, causes a severe case of compound heterozygous OPPG. We undertake 3D homology modeling of the four extracellular YWTD b-propeller/EGF-like domains (E1-E4) of LRP5, and show that both novel mutations destabilize the b-propeller domains that are critical for protein and ligand binding to regulate Wnt signaling and osteoblast function. Although AFFs have been reported in other rare bone diseases, this is the first in a genetic condition of primary osteoblast dysfunction. The relatively low bone turnover observed, and knowledge of LRP5 function, implicates impaired bone remodeling in the pathogenesis of AFF.

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Section: Introductionmentioning

confidence: 99%

Atypical Femoral Fracture in Osteoporosis Pseudoglioma Syndrome Associated with Two Novel Compound Heterozygous Mutations in LRP5

Alonso

Soares

McCloskey

et al. 2014

Journal of Bone and Mineral Research

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“…the elderly or HIV positive. In prenatal infections it can lead to loss of hearing and is also connected to congenital blindness [28].…”

Section: Introductionmentioning

confidence: 99%

Intracellular imaging of host‐pathogen interactions using combined CARS and two‐photon fluorescence microscopies

Robinson

Ochsenkühn

Campbell

et al. 2010

Journal of Biophotonics

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Intracellular imaging is a key tool in the investigation of host-pathogen interactions. Advances in this area are particularly sought to understand the effect of viral infection processes on the host cell and its metabolic functions including those cases where host cell lipid metabolism is modulated as a result of infection. We demonstrate the use of combined coherent anti-Stokes Raman scattering (CARS) and two-photon fluorescence microscopies to image fibroblast cells infected by cytomegalovirus. CARS is used to image the host cell membrane, lipid droplets and morphology of the nucleus. Cell nuclei are found to expand during infection, approximately doubling in area. Some cells also show accumulations of lipid droplets at the nuclear periphery. Using a genetically modified virus strain expressing the green fluorescent protein also enables two-photon imaging of the same cells to reveal the location, nature and extent of viral protein expression.

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“…OPPG is characterized by extremely low bone mass at young ages and a high propensity for bone fractures. OPPG patients also suffer from vision problems related to several factors that affect the ability of the retina to develop normal vascularization (107).…”

Section: E Lrp5mentioning

confidence: 99%

Low-Density Lipoprotein Receptor-Related Proteins in Skeletal Development and Disease

Yang

Williams

2017

Physiological Reviews

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The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction. This review is focused on the roles of selected members of this protein family in skeletal development and disease. We present background on the identification of this subgroup of receptors, discuss the phenotypes associated with alterations in their function in human patients and mouse models, and describe the current efforts to therapeutically target these proteins to treat human skeletal disease.

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Congenital blindness and osteoporosis-pseudoglioma syndrome

Cited by 15 publications

References 6 publications

Atypical Femoral Fracture in Osteoporosis Pseudoglioma Syndrome Associated with Two Novel Compound Heterozygous Mutations in LRP5

Atypical Femoral Fracture in Osteoporosis Pseudoglioma Syndrome Associated with Two Novel Compound Heterozygous Mutations in LRP5

Intracellular imaging of host‐pathogen interactions using combined CARS and two‐photon fluorescence microscopies

Low-Density Lipoprotein Receptor-Related Proteins in Skeletal Development and Disease

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