Novel 23-base-pair duplication mutation in TSC1 exon 15 in an infant presenting with cardiac rhabdomyomas

Abstract

Tuberous sclerosis is a dominantly inherited disorder due to mutations at two gene loci, the TSC1 locus on chromosome 9q34 and the TSC2 locus on chromosome 16p13.3. The TSC2 and the TSC1 genes have now been cloned, enabling mutation analysis. We report results of mutation analysis in a sporadic case of TSC first identified in intra-uterine life on the basis of the presence of cardiac rhabdomyomas. Postnatally this infant was also found to have subependymal nodules on brain computed tomographic scan. Hypomelanotic macules were not detected neonatally or at 12 months of age. The specific TSC1 exon 15 mutation found in our patient has not previously been reported in cases of TSC. This mutation involves duplication of a 23- bp segment of DNA between two 9-bp repeated sequence elements within exon 15. These repeat elements are located between nucleotides 1892-1900 and between nucleotides 1915-1923 within the TSC1 gene sequence. It is likely that the presence of these two repeated elements predisposes to misalignment of DNA strands and unequal crossing over. The mechanism of origin of rhabdomyomas in TSC is reviewed. Loss of heterozygosity in the TSC gene regions has been reported in cardiac rhabdomyomas; however, these lesions are self-limiting in their growth. The basis for this self limiting proliferation is not clear. One interesting postulation is that cardiac rhabdomyomas may be due to delay or failure of apoptosis which occurs as part of the normal remodeling process in the heart.

Links

PhilArchive



    Upload a copy of this work     Papers currently archived: 92,410

External links

Setup an account with your affiliations in order to access resources via your University's proxy server

Through your library

  • Only published works are available at libraries.

Similar books and articles

Genetic disease, genetic testing and the clinician.Kelly C. Smith - 2001 - Journal of the American Medical Association 285 (1):91.

Analytics

Added to PP
2017-04-03

Downloads
0

6 months
0

Historical graph of downloads

Sorry, there are not enough data points to plot this chart.
How can I increase my downloads?

Citations of this work

No citations found.

Add more citations

References found in this work

No references found.

Add more references