SOX18 mutations in humans are associated with both recessive and dominant hypotrichosis–lymphedema–telangiectasia syndrome (HLTS). We report two families with affected children carrying a SOX18 mutation: a living patient and his stillborn brother from Canada and a Belgian patient. The two living patients were diagnosed with HLTS and DNA analysis for the SOX18 gene showed that both had the identical heterozygous C > A transversion, resulting in a pre-mature truncation of the protein, lacking the transactivation domain. Both living patients developed renal failure with severe hypertension in childhood for which both underwent renal transplantation. To our best knowledge this is the first report of renal failure associated with heterozygous mutations in the SOX18 gene. We conclude that this specific mutation results in a new, autosomal dominant condition and propose the acronym HLT-renal defect syndrome for HLTRS.
Francois Mathias, Koopman Peter, Beltrame Monica, SoxF genes: Key players in the development of the cardio-vascular system, 10.1016/j.biocel.2009.08.017
François Mathias, Caprini Andrea, Hosking Brett, Orsenigo Fabrizio, Wilhelm Dagmar, Browne Catherine, Paavonen Karri, Karnezis Tara, Shayan Ramin, Downes Meredith, Davidson Tara, Tutt Desmond, Cheah Kathryn S. E., Stacker Steven A., Muscat George E. O., Achen Marc G., Dejana Elisabetta, Koopman Peter, Sox18 induces development of the lymphatic vasculature in mice, 10.1038/nature07391
Oliver Guillermo, Wigle Jeffrey T., Chowdhury Kamal, Gruss Peter, 10.1038/6844
Downes Meredith, François Mathias, Ferguson Charles, Parton Robert G., Koopman Peter, Vascular defects in a mouse model of hypotrichosis-lymphedema-telangiectasia syndrome indicate a role for SOX18 in blood vessel maturation, 10.1093/hmg/ddp219
Irrthum Alexandre, Devriendt Koenraad, Chitayat David, Matthijs Gert, Glade Conrad, Steijlen Peter M., Fryns Jean-Pierre, Van Steensel Maurice A. M., Vikkula Miikka, Mutations in the Transcription Factor Gene SOX18 Underlie Recessive and Dominant Forms of Hypotrichosis-Lymphedema-Telangiectasia, 10.1086/375614
Proesmans Willem, Legius Eric, Van Herck Karina, Van Damme Boudewijn, Cutaneous telangiectasia, sparse hair and membranoproliferative glomerulonephritis : A new case of a newly recognized entity, 10.1007/bf00852899
Alders Marielle, Hogan Benjamin M, Gjini Evisa, Salehi Faranak, Al-Gazali Lihadh, Hennekam Eric A, Holmberg Eva E, Mannens Marcel M A M, Mulder Margot F, Offerhaus G Johan A, Prescott Trine E, Schroor Eelco J, Verheij Joke B G M, Witte Merlijn, Zwijnenburg Petra J, Vikkula Mikka, Schulte-Merker Stefan, Hennekam Raoul C, Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans, 10.1038/ng.484
Gupta I. R., Tsai C. H., Siegel-Bartelt J., Thorner P., Balfe J. W., Cutaneous telangiectasias, sparse hair, and type I membranoproliferative glomerulonephritis, 10.1007/s004670050578
Sherwood M C, Pincott J R, Goodwin F J, Dillon M J, Dominantly inherited glomerulonephritis and an unusual skin disease., 10.1136/adc.62.12.1278
Gimelli Stefania, Caridi Gianluca, Beri Silvana, McCracken Kyle, Bocciardi Renata, Zordan Paola, Dagnino Monica, Fiorio Patrizia, Murer Luisa, Benetti Elisa, Zuffardi Orsetta, Giorda Roberto, Wells James M., Gimelli Giorgio, Ghiggeri Gian Marco, Mutations in SOX17 are associated with congenital anomalies of the kidney and the urinary tract, 10.1002/humu.21378
Hoeth Martina, Niederleithner Heide, Hofer-Warbinek Renate, Bilban Martin, Mayer Herbert, Resch Ulrike, Lemberger Christof, Wagner Oswald, Hofer Erhard, Petzelbauer Peter, de Martin Rainer, The Transcription Factor SOX18 Regulates the Expression of Matrix Metalloproteinase 7 and Guidance Molecules in Human Endothelial Cells, 10.1371/journal.pone.0030982
McGuire John K., Harju-Baker Susanna, Rims Cliff, Sheen Joong-Hyuk, Liapis Helen, Matrilysin (MMP-7) Inhibition of BMP-7 Induced Renal Tubular Branching Morphogenesis Suggests a Role in the Pathogenesis of Human Renal Dysplasia, 10.1369/0022155411435152
Bibliographic reference
Moalem, S. ; Brouillard, Pascal ; Kuypers, D. ; Legius, E. ; Harvey, E. ; et. al. Hypotrichosis-lymphedema-telangiectasia-renal defect associated with a truncating mutation in the SOX18 gene. In: Clinical Genetics, Vol. 87, no. 4, p. 378-82 (2015)