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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-39530

Isidor, B; Pichon, O; Redon, R; Day-Salvatore, D; Hamel, A; Siwicka, K A; Bitner-Glindzicz, M; Heymann, D; Kjellén, L; Kraus, C; Leroy, J G; Mortier, G R; Rauch, A; Verloes, A; David, A; Le Caignec, C (2010). Mesomelia-synostoses syndrome results from deletion of SULF1 and SLCO5A1 genes at 8q13. American Journal of Human Genetics, 87(1):95-100.

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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. So far, five patients in four unrelated families have been reported worldwide with MMS. By using whole-genome oligonucleotide array CGH, we have identified an 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 whereas the function of SLCO5A1 is yet unknown. Breakpoint sequence analyses performed in two families showed nonrecurrent deletions. Real-time quantitative RT-PCR analysis showed the highest levels of SULF1 transcripts in human osteoblasts and cartilage whereas SLCO5A1 was highly expressed in human fetal and adult brain and heart. Our results strongly suggest that 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--was found in all patients, so we suggest that 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.


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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Medical Genetics
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Deposited On:12 Jan 2011 15:49
Last Modified:05 Apr 2016 14:26
Publisher:American Society of Human Genetics
Additional Information:555
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.1016/j.ajhg.2010.05.012
PubMed ID:20602915

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