Tuberous sclerosis in a 19-week fetus: immunohistochemical and molecular study of hamartin and tuberin.
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.
Department of Pathology, New York University School of Medicine, 560 First Avenue, New York, NY 10016, USA.
Jianjun
J
Wei
Peng
P
Li
Luis
L
Chiriboga
Masashi
M
Mizuguchi
Herman
H
Yee
Douglas C
DC
Miller
M Alba
MA
Greco
D000328:Adult; D000818:Animals; D004247:DNA / Q000032:analysis; D005260:Female; D016147:Genes, Tumor Suppressor; D006338:Heart Neoplasms / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D012097:Repressor Proteins / Q000378:metabolism*; D012207:Rhabdomyoma / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D014402:Tuberous Sclerosis / Q000378:metabolism* / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D004247:DNA