PS-076 Novel Mutations Underlying Rare Familial Enteropathies

Abstract

Background Microvillous Inclusion Disease (MVID) and Congenital Tufting Enteropathy (CTE) are congenital disorders of the intestinal epithelial cells that cause an intractable diarrhoea since birth. MVID and CTE are very rare disorders and inherited as autosomal recessive traits. Recently, mutations of MYO5B and EpCAM were identified as the underlying lesion resulting in MVID and CTE, respectively. Method Four Saudi families were investigated, three with children affected by MVID and one with a child affected by CTE. Five patients and available unaffected individuals were subjected to genome-wide homozygosity scans using the Affymetrix 250K SNP array. Analysis with the copy number tool CNAG identified shared homozygous regions unique to the affected subjects. Results Of the three families with MVID, homozygosity was observed in two families at a locus on chromosome 18 which included MYO5B . Sequencing of MYO5B in individuals from these families identified two novel nonsense mutations in exons 24 and 36 (Q1047X and E1589X). In the other family homozygosity was absent at the MYO5B locus. However, a locus on chromosome 2 which included EpCAM was found to be homozygous in this family. Sequencing of EpCAM identified a 1 bp insertion (c.499insC) in exon 5 resulting in premature truncation of the mature protein. This was consistent with this family being classified as having CTE rather than MVID. The fourth family studied was referred with a diagnosis of CTE and was found to have the same 1 bp insertion consistent with a common founder. Conclusion We have identified novel nonsense mutations in MYO5B and EpCAM associated with congenital enteropathies in Saudi families. Our findings expand the limited spectrum of MYO5B and EpCAM mutations associated with gastrointestinal genetic disorders and provide an opportunity to investigate phenotype/ genotype correlations.