435ae0f2-2ee0-425a-bdff-6a0628ed381f
title
Evaluation of the role of the  SQSTM1  gene in sporadic Belgian patients with Paget's disease.
97af01e4-3ede-4eb7-9e93-0bfcf300cdfc
abstract
A positional cloning effort in French Canadian families with Paget's disease of bone (PDB) resulted in the identification of a mutation in the  sequestosome1  ( SQSTM1 ) gene in a subset of both familial and sporadic PDB cases. This was confirmed in samples of mainly United Kingdom (UK) origin. In this study, we performed both mutation analysis and association studies in order to evaluate the role of this gene in a collection of isolated Belgian PDB patients. A mutation in the  SQSTM1  gene was found in only 6 of 111 patients (5.4%). In all cases it involves the  P392L  mutation, previously shown to be common in both familial and sporadic cases. To perform association studies, we selected 8 single nucleotide polymorphisms (SNPs) and looked for linkage disequilibrium (LD) between these. Haplotype analysis indicated that typing of 3 Tag SNPs ( IVS1 + 633A/C ,  IVS5 - 23A/G , and  976A/G ) enables us to identify the most common haplotypes. Association studies for the 3 selected SNPs, based on 105 PDB cases without a  SQSTM1  mutation and 159 control individuals, did not support a possible influence of natural variants in the  SQSTM1  gene either on the pathogenesis of PDB or on the disease severity. In conclusion, our study confirms that the  P392L  mutation is a recurrent mutation causing PDB in different populations. We were not able to show an association between  SQSTM1  polymorphisms and PDB in our population but this clearly needs to be extended to other populations. The presented identification of haplotype Tag SNPs will be of major help for such studies.