Measuring TMPRSS6 expression to clarify genetic diagnosis in IRIDA

Iron-refractory iron deficiency anemia (IRIDA) is generally considered to be an
autosomal recessive congenital disorder. However, some patients with only a
mono-allelic TMPRSS6 defect also show an IRIDA phenotype, while other
heterozygotes stay healthy. Even within families, there is not always a clear
genotype-phenotype correlation. Possibly, due to influences of other genetic
factors, the expression of TMPRSS6 may vary between people, even when they have
the same TMPRSS6 genotype. We hypothesize that the TMPRSS6 expression level is
related to the presence and the severity of the IRIDA phenotype. If this is
true, testing the expression level may be used in diagnosis, especially in case
of heterozygosity.

(Primary) Determine whether measuring the expression level is a good functional
test for confirming the genetic diagnosis in IRIDA by establishing the relation
between the TMPRSS6 mRNA expression and the phenotype in IRIDA patients and
their family members.
(Secondary) Get more insight into the role of additional genetic factors in
causing IRIDA by determining the relation between the TMPRSS6 mRNA expression
and the TMPRSS6 genotype in IRIDA patients and their family members.

Invasive observational study. We use EBV-immortalized lymphoblast cell lines to
determine TMPRSS6 expression and medical data to determine IRIDA phenotype and
genotype of subjects.

A total of 11 ml blood will be collected from all subjects by a single
venipuncture. Venipuncture is a routine procedure with minimal burden and
risks. Results from earlier laboratory tests and physical examination will be
used as well. Since the study is observational, there will be no direct
benefits for subjects. However, the results will provide new insight into the
pathophysiology of IRIDA and may improve the diagnosis of IRIDA, especially in
case of a heterozygous TMPRSS6 defect. This can also be relevant for the
subjects.