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Gene: LRP5

Green List (high evidence)

Strong gene-disease association.
Osteoporosis-pseudoglioma: blindness caused by ocular defects, as well as childhood onset of osteoporosis, reduced bone mineral density, and recurrent fractures. Additional features can include microphthalmos, moderate intellectual disability, short stature, joint laxity, and/or hypotonia.

Exudative vireoretinopathy: subset condition - when AR, generally early onset and severity of features, visual problems ranging from peripheral visual disturbances to blindness in some cases, as well as reduced bone mineral density and a predisposition to fractures.

However, complexity in variant spectrum and cause of associated phenotypes.
Biallelic LoF/null variants cause osteoporosis-pseudoglioma syndrome,
Biallelic missense can cause exudative vireoretinopathy (AR - PMID: 9056564, 15346351, 9831343),
Heterozygous missense can cause osteopetrosis (AD phenotype) and incomplete penetrance reported.
Some of the disease-causing LRP5 variants overlap between cases with different diagnoses.
Functional studies also available.

Created: 11 Sep 2024, 3:52 a.m. | Last Modified: 11 Sep 2024, 3:52 a.m.

Panel Version: 1.287

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
Exudative vitreoretinopathy 4 MIM#601813; Osteoporosis-pseudoglioma syndrome MIM#259770

Publications

• 9056564 9831343 11719191 15346351 18602879