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We identified a family in which a previously unknown genetic association between coeliac disease (CD) and mutation of factor V (factor V Leiden) occurred. The index case was a young woman who abruptly presented with severe ascites due to Budd-Chiari syndrome. At endoscopy, she presented with a scalloped duodenal mucosa suggestive of CD, further confirmed by histology and serological tests. Haematological assessment unveiled the mutation of factor V due to the Arg506→Gln mutation at position 506.1 As shown in fig 1⇓, five siblings were also found to be affected by CD (histology performed in all cases) and were heterozygous carriers of factor V Leiden for the same mutation. The two diseases segregated as one in all cases while no sibling was affected by only one of the two diseases. This pattern of inheritance strongly suggests that the genetic mutation responsible for the onset of CD in this family occurs in a gene which is in high linkage disequilibrium with factor V gene, which is sited on the long arm of chromosome 1. The penetrance of such a gene in our family was found to be 100% as all of the carriers demonstrated coeliac disease at endoscopy.
Although susceptibility to CD is strongly determined by environmental gluten, it is clearly a common genetic disorder. HLA-DQ2 and HLA-DQ8 located in the MHC region on chromosome 6 have been related to a genetic predisposition to CD, although these genes are also present in those not affected by CD.2 The association between coeliac disease and factor V Leiden in the present family is strongly suggestive of the presence of a gene in linkage disequilibrium with the long arm of chromosome 1 which is able to trigger the development of CD in all carriers. We feel that further studies are needed to identify such a gene in order to unravel the pathogenesis of CD. Moreover, further assessment of the degree of association between CD and factor V Leiden may be clinically important to avoid severe episodes of thromboembolism as that which occurred in our patient.
Conflict of interest: None declared.
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