Molecular studies in a family with eosinophilic esophagitis (EoE)

EoE is a rapidly increasing disorder which usually presents with dysphagia. The
pathophysiology remains largely unexplained. An allergic pathway is suggested
by the observation that a large proportion of EoE patients has an atopic
constitution and elementary diets have been shown to have a beneficial effect.
Familial clustering indicates that genetic factors play a role as well in the
pathophysiology. EoE shows a sibling risk ratio (*S) of approximately 80, which
is high compared to other atopic diseases such as asthma (*S about 2).
So far, only few Genome Wide Association Studies (GWAS) have been performed
aiming to identify loci associated with EoE. GWAS have shown associations with
CCL26 (encoding for eotaxin-3) in 14% of EoE patients, and with TGFB1, TSLP,
and FLG in smaller percentages of patients. No replication studies have yet
been performed to confirm these associations. No pathological mutations have
been described in EoE patients.
We reason that performing molecular analyses in a well-defined family with
multiple affected members with EoE may allow identification of genes associated
with EoE, especially if linkage and sequencing studies are combined.

1) To identify chromosomal regions associated with the EoE-phenotype in a
family with multiple affected family members. Subsequently these regions will
be sequenced to detect causative gene(s).
2) To describe the clinical characteristics of EoE-patients within this family.

We will perform linkage analysis in one family with EoE-patients in multiple
generations. Suggestive chromosomal regions identified by linkage analysis will
be further investigated by Sanger sequencing or next generation sequencing,
depending on the number and the size of the identified regions.
Clinical information will be obtained from a questionnaire.

Peripheral blood drawing will be performed once and does not bring along any
mentionable risks
Filling out the questionnaire will take 20 minutes.