Sunday 11 July 2010
Mesomelia-synostoses syndrome (MSS) or mesomelic dysplasia with acral synostoses Verloes-David-Pfeiffer type is a rare autosomal-dominant disorder characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations.
interstitial deletion at 8q13 in all patients
- The deletions vary from 582 Kb to 738 Kb in size, but invariably encompass only two genes: SULF1, encoding the heparan sulfate 6-O-endosulfatase 1, and SLCO5A1, encoding the solute carrier organic anion transporter family member 5A1.
- SULF1 acts as a regulator of numerous growth factors in skeletal embryonic development.
- The function of SLCO5A1 is yet unknown.
- Highest levels of SULF1 transcripts are found in human osteoblasts and cartilage.
- SLCO5A1 is highly expressed in human fetal and adult brain and heart.
- haploinsufficiency of SULF1 contributes to this mesomelic chondrodysplasia, highlighting the critical role of endosulfatase in human skeletal development.
- Codeletion of SULF1 and SLCO5A1—which does not result from a low-copy repeats (LCRs)-mediated recombination event in at least two families—is found in all patients.
- Haploinsufficiency of SULF1 combined with haploinsufficiency of SLCO5A1 (or the altered expression of a neighboring gene through position effect) could be necessary in the pathogenesis of MSS.
Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13. Isidor B, Pichon O, Redon R, Day-Salvatore D, Hamel A, Siwicka KA, Bitner-Glindzicz M, Heymann D, Kjellén L, Kraus C, Leroy JG, Mortier GR, Rauch A, Verloes A, David A, Le Caignec C. Am J Hum Genet. 2010 Jul 9;87(1):95-100. PMID: #20602915#