Rapamycin has gained significant attention for its potential activity in reducing the size of TSC-associated tumors, thus providing alternative to surgery. This study aimed at determining the efficacy of rapamycin and rapalogs for reducing the size of TSC-associated solid tumors in patients with Tuberous Sclerosis Complex (TSC).
Although routine screening for primary aldosteronism (PA) is increasingly recognized among patients with obstructive sleep apnea (OSA), data regarding aldosterone-to-renin ratio (ARR) screening positivity among Southeast Asian OSA populations remain limited, particularly in resource-limited settings. This study aimed to determine the prevalence and clinical correlates of ARR positivity screening among obese hypertensive OSA patients. In this cross-sectional study, obese hypertensive adults with confirmed OSA were recruited. Blood samples were analyzed for plasma aldosterone concentration (PAC), plasma renin concentration (PRC), serum potassium, and standard metabolic indices. Therapeutic intensity score (TIS) was used to quantify antihypertensive burden. ARR-based categories were applied to stratify patients into (i) positive ARR (Group 1), (ii) low renin/negative ARR (Group 2), or (iii) negative ARR (Group 3). Among 160 patients, 11.9% were classified in Group 1 and 20.0% as Group 2. Serum potassium levels were significantly lower in Group 2 compared with Group 3. An inverse association between PRC and uric acid was observed in the overall cohort, although the model fit was weak. In males, serum potassium, uric acid, and TIS were significantly associated with RAAS activity and were associated with greater likelihood for ARR positive screen. A substantial proportion of obese hypertensive OSA patients demonstrated ARR positivity. However, routine clinical and metabolic parameters alone were insufficient to reliably identify affected individuals. These findings support maintaining a low threshold for PA screening in hypertensive OSA patients.
Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder characterized by tumor growth in multiple organs and caused by mutations in either TSC1 or TSC2 genes. Because of their relatively large genomic sizes, absence of hotspots, and common type of mutations, mutation detection in TSC1 and TSC2 genes has been challenging. We devised a combination of multiple ligation-dependent probe amplification (MLPA) and amplicon sequencing (AS) to simplify the detection strategy, yet we come up with reasonably high detection rate. Thirty-four Malaysian patients diagnosed with TSC were referred to Human Genome Center, Universiti Sains Malaysia. We used a combination of MLPA to detect large copy number changes and AS to detect smaller mutations. TSC1 pathogenic or likely pathogenic mutations were found in 6 patients (18%) and TSC2 in 21 patients (62%), whereas 6 patients (18%) show no mutations and 1 patient (2%) showed only TSC2 missense variant with uncertain significance. Six of the mutations are novel. Our detection strategy costs 81% less and require 1 working week less than the conventional strategy. Confirmatory sequencing using Sanger method on a few representative mutations showed agreement with results of the AS. Combination of MLPA and Illumina MiSeq AS provides a simplified strategy and reasonably high detection rate for TSC1/TSC2 mutation, which suggested application of the strategies into clinical molecular diagnostics.
Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder affecting multiple organs. Tuberous sclerosis complex is caused by mutation in either one of the two disease-causing genes, TSC1 or TSC2, encoding for hamartin and tuberin, respectively. TSC2/PKD1 contiguous gene deletion syndrome is a very rare condition due to deletion involving both TSC2 and PKD1 genes. Tuberous sclerosis complex cannot be easily diagnosed since there is no pathognomonic feature, although there are consensus diagnostic criteria for that. Mutation analysis is useful and plays important roles. We report here two novel gross deletions of TSC2 gene in Malay patients with tuberous sclerosis complex and TSC2/PKD1 contiguous gene deletion syndrome, respectively.