Tuberous sclerosis complex (
TSC) is a genetically heterogeneous disease caused by mutations of TSC1 or TSC2 genes. It involves multiple organ systems resulting in mild to lethal
hamartoma formation due to gene mutation in the germ line and loss of heterozygosity (LOH) in somatic cells.
Hamartin (TSC1) and
tuberin (TSC2) are expressed broadly. However, little is known about tissue susceptibility to
hamartomas when equal or similar amounts of
TSC gene expression are present. In this study, we present a 19-week gestational age fetus with pathological features of
TSC, which was confirmed by finding LOH of TSC2 in a cardiac
rhabdomyoma. Developmental expression of
hamartin and
tuberin in the
TSC fetus, an age-matched non-
TSC fetus, and a 26-week gestational age non-
TSC fetus were analyzed by immunohistochemistry. We found that in addition to the differential expression of the
TSC genes in some normal tissues compared with that in the
TSC-affected fetus, the cellular localization and distribution of
hamartin and
tuberin were dramatically different in different tissues. In general,
hamartin and
tuberin are mainly expressed in epithelial cells, myocytes, and neural tissues. By comparing the incidence of the
hamartomas in early childhood and gene expression in tissues, it appears that tissues with co-expression of
hamartin and
tuberin are prone to a higher incidence of
hamartomas than those expressing only one
protein, or two
proteins but in different patterns of cellular localization.