Abstract
Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by lacrimal duct aplasia, malformed ears and deafness, small teeth and digital anomalies. We identified heterozygous mutations in the tyrosine kinase domains of the genes encoding fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3) in LADD families, and in one further LADD family, we detected a mutation in the gene encoding fibroblast growth factor 10 (FGF10), a known FGFR ligand. These findings increase the spectrum of anomalies associated with abnormal FGF signaling.
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Acknowledgements
We are thankful to all family members that participated in this study, M. Langen for excellent technical assistance and I. Feenstra and D. Koolen for sample collection and clinical analysis. This work was supported in part by the Turkish Academy of Sciences, in the framework of the Young Scientist Award Program (BW/TUBA-GEBIP/2002-1-20), European Commission FP6 Integrated Project EUROHEAR, LSHG-CT-20054-512063, US National Institutes of Health grants RO1-AR051448 and RO1-AR051886 to J.S., and the German Federal Ministry of Science and Education through the National Genome Research Network (G.N., C.B. and P.N.).
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Supplementary information
Supplementary Fig. 1
Mapping the LADD1 locus. (PDF 83 kb)
Supplementary Fig. 2
FGFR2, FGFR3 and FGF10 mutations in LADD syndrome. (PDF 138 kb)
Supplementary Fig. 3
Locations of the LADD mutations in the tyrosine kinase domains of FGFR2, FGFR3 and FGF10. (PDF 635 kb)
Supplementary Table 1
Single and additive two-point LOD scores of 10q26 markers. (PDF 19 kb)
Supplementary Table 2
Primers used for mutation screening in LADD syndrome. (PDF 21 kb)
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Rohmann, E., Brunner, H., Kayserili, H. et al. Mutations in different components of FGF signaling in LADD syndrome. Nat Genet 38, 414–417 (2006). https://doi.org/10.1038/ng1757
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DOI: https://doi.org/10.1038/ng1757
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