Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder marked by hamartoma growth in multiple organ systems. We performed mutational analyses on 325 individuals with definite tuberous sclerosis complex diagnostic status. We identified mutations in 72% (199/257) of de novo and 77% (53/68) of familial cases, with 17% of mutations in the TSC1 gene and 50% in the TSC2 gene. There were 4% unclassified variants and 29% with no mutation identified. Genotype/phenotype analyses of all observed tuberous sclerosis complex findings in probands were performed, including several clinical features not analyzed in two previous large studies. We showed that patients with TSC2 mutations have significantly more hypomelanotic macules and learning disability in contrast to those with TSC1 mutations, findings not noted in previous studies. We also observed results consistent with two similar studies suggesting that individuals with mutations in TSC2 have more severe symptoms. On performing meta-analyses of our data and the other two largest studies in the literature, we found significant correlations for several features that It has alternative splice sites at two exons (25 and 31) to create isoforms. 4,5 Tuberin has a calculated molecular weight of approximately 200 kD coding from a transcript of approximately 5.5 kb. The TSC1 gene was discovered a decade after the initial report of linkage (Online Mendelian Inheritance in Man 191100). 6 In contrast with the TSC2 gene, the TSC1 gene has 23 exons extending over approximately 55 kb of genomic DNA on chromosome 9q34.3. The TSC1 gene product is coded from exons 3 to 23. Noncoding sequences include exons 1 and 2, and a 4.5-kb 3= untranslated region. The protein product of the TSC1 gene (hamartin) has an estimated molecular weight of 130 kD coding from an 8.6-kb mRNA transcript. To date, more than 680 disease-causing mutations have been identified in either the TSC1 or TSC2 genes. 7 Approximately 70% to 80% of individuals who meet definite diagnostic criteria have a small identifiable TSC1 or TSC2 gene mutation. The remaining individuals probably have large gene deletions, somatic mosaic mutations, and mutations in unanalyzed gene noncoding regions, rather than an additional TSC gene locus.Of interest is whether the phenotypic presentation of TSC differs by whether the disease results from mutations in TSC1 or TSC2. Early studies reporting genotype/phenotype correlations did not find evidence for phenotypic differences between patients with TSC1 mutations and patients with no mutation identified

Tuberous sclerosis complex is an autosomal dominant disease of benign tumors occurring in multiple organ systems of the body. Either of two genes, TSC1 or TSC2, can be mutated, resulting in the tuberous sclerosis complex phenotype. The protein products of the tuberous sclerosis complex genes, hamartin (TSC1) and tuberin (TSC2), have been discovered to play important roles in several cell-signaling pathways. Knowledge regarding the function of the tuberin-hamartin complex has led to therapeutic intervention trials. Numerous pathogenic mutations have been elucidated in individuals affected with tuberous sclerosis complex. Information on the type and distribution of nearly 1000 mutations in the two genes is discussed. Mosaicism for tuberous sclerosis complex mutations has been documented, complicating provision of genetic counseling to families. Emerging genotype-phenotype correlations should provide guidance for better medical care of individuals with tuberous sclerosis complex.

This study sought to identify if differences existed in risk comprehension and risk format understanding between genetic counseling patients of Hispanic and Caucasian ethnicity. A total of 107 questionnaires were collected, 56 from Hispanic patients, and 51 from Caucasian controls. Of the total population 41.1% (44/107) could not demonstrate sufficient risk understanding, which was 71.4% (40/56) of Hispanics and 7.8% (4/51) of Caucasians. Fractions were the best-understood format for all participants. However, both Hispanics and Caucasians had difficulties with the percentage risk format. Discrepancies were also noted in qualitative word format understanding. Awareness of differences in risk comprehension may affect the selection of counseling techniques and strategies utilized by genetic counselors when educating patients about risk related information.

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