Molecular studies in a multigenerational family with gastro-esophageal reflux disease (GERD)

Gastro-esophageal reflux disease (GERD) is a common disease in adults and
chilren. The pathophysiology of GERD is largely unknown and is probably
multifactorial. However, the reported familial clustering and high prevalence
of GERD in twins indicate that genetic factors are likely to play a role as
well in its pathophysiology. In families with GERD only a few linkage studies
have been performed aiming to identificate genes that are associated with a
GERD phenotype. Linkage analysis in a family with pediatric GERD by Hu et al.
showed a linked region on chromosome 13q14.Subsequently conducted studies, did
not succeed in replication of linkage to this region nor in identification of a
susceptibility gene for GERD in this region. More recently, genome wide linkage
analysis in four different patient cohorts followed by an association study and
protein analysis identified COL3A1, a gene located on chromosome 2 and
responsible for the synthesis of the protein collagen type 3, as a
susceptibility locus for GERD.
No replication studies have yet been performed to confirm this possible
association. To conclude, up till now no genes have been confirmed to be
associated with GERD.
Performing molecular analyses in well-defined large families may allow
identification of genes associated with GERD, especially if linkage and
sequencing studies are combined. This should lead to increased insight in the
pathophysiology of this common disease.

To identify chromosomal regions associated with the GERD-phenotype in a large
multigenerational family with multiple affected members. Subsequently these
regions will be sequenced to detect causative gene(s). The second aim is to
describe the clinical characteristics of GERD within this family (the
phenotype).

Linkage analysis will be performed in one large multigenerational family.
Suggestive chromosomal regions identified in this way will be further
investigated by sequencing, either Sanger sequencing or Next Generation
Sequencing, depending on number and size of the identified regions.
Furthermore, clinical information will be obtained by a questionnaire and from
files.

Participating patients will not be subjected to invasive investigations.
Filling out the questionnaire will take about 10 minutes of their time.
Peripheral blooddrawing or taking saliva samples does not bring along
noteworthy risks.