title: Tuberous sclerosis complex without tubers and subependymal nodules: a phenotype-genotype study.
abstract: Tuberous sclerosis complex (TSC) is caused by a mutation in the TSC1 or TSC2 genes. However, 15% of patients have no mutation identified. Tubers and subependymal nodules (SENs) are the typical brain lesions in TSC and are present in 90-95% of patients. The objective of this study is to characterize the specific genotype-phenotype of patients without these lesions. We analyzed the features of 11 patients without typical TSC neuroanatomic features. Ten had TSC1/TSC2 mutational analysis, which was negative. Clinically they had lesions thought to be of neural crest (NC) origin, such as hypomelanotic macules, facial angiofibromas, cardiac rhabdomyomas, angiomyolipomas, and lymphangioleiomyomatosis. We hypothesize that patients without tubers and SENs reflect mosaicism caused by a mutation in TSC1 or TSC2 in a NC cell during embryonic development. This may explain the negative results in TSC1 and TSC2 testing in DNA from peripheral leukocytes.
authors.affiliation: Department of Neurology, Herscot Center for TSC, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatric Neurology, Vall d' Hebron Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Boronat
authors.forename: E A
authors.initials: EA
authors.lastname: Shaaya
authors.forename: C M
authors.initials: CM
authors.lastname: Doherty
authors.forename: P
authors.initials: P
authors.lastname: Caruso
authors.forename: E A
authors.initials: EA
authors.lastname: Thiele
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D014402:Tuberous Sclerosis / Q000235:genetics*; D055815:Young Adult
keywords: mosaicism; neural crest; no mutation identified (NMI); tuberous sclerosis complex (TSC)