@article {621,
	title = {Mutations in the fourth β-propeller domain of LRP4 are associated with isolated syndactyly with fusion of the third and fourth fingers.},
	journal = {Hum Mutat},
	volume = {39},
	year = {2018},
	month = {2018 06},
	pages = {811-815},
	abstract = {<p>Isolated hand syndactyly is a common limb malformation with limited known genetic etiology. We used exome sequencing to discover two novel variants, chr11 g.46896373C>G; p.D1403H and chr11 g.46893078G>T; p.Q1564K, in LRP4 in a child with isolated bilateral syndactyly of the third and fourth fingers. Each variant was inherited from a different parent and neither parent was affected. Variants in LRP4 have been previously associated with syndactyly in Cenani-Lenz syndactyly syndrome and Sclerosteosis 2, but have not been reported in individuals with isolated syndactyly. LRP4 inhibits LRP6/LRP5-mediated activation of canonical Wnt signaling and mediates sclerostin-dependent inhibition of bone formation. p.D1403H and p.Q1564K are located within the fourth β-propeller of the extracellular protein domain that has yet to be associated with human disease. Functional analyses of p.D1403H and p.Q1564K show that they significantly decrease LRP4{\textquoteright}s inhibition of Wnt signaling. These results suggest that variants in the fourth β-propeller of the extracellular protein domain may cause a phenotype distinct from previously characterized LRP4 variants.</p>},
	issn = {1098-1004},
	doi = {10.1002/humu.23417},
	author = {Sukenik Halevy, Rivka and Chien, Huan-Chieh and Heinz, Bo and Bamshad, Michael J and Nickerson, Deborah A and Kircher, Martin and Ahituv, Nadav}
}
