Thomas N Darling

Learn More
BACKGROUND The Proteus syndrome is characterized by the overgrowth of skin, connective tissue, brain, and other tissues. It has been hypothesized that the syndrome is caused by somatic mosaicism for a mutation that is lethal in the nonmosaic state. METHODS We performed exome sequencing of DNA from biopsy samples obtained from patients with the Proteus(More)
Proteus syndrome is a rare and highly variable hamartomatous syndrome that can affect multiple organ systems. It is characterized by hyperplastic lesions of connective tissue, vascular malformations, linear verrucous epidermal nevi, and hyperostoses. The cause of the disorder is unknown, but the current working hypothesis is that it is caused by a mosaic(More)
BACKGROUND Birt-Hogg-Dubé syndrome (BHD) is a dominantly inherited predisposition for development of fibrofolliculomas, trichodiscomas, and acrochordons. Concurrent internal tumors, such as colonic polyps and renal carcinoma, have been described in patients with BHD. OBJECTIVE To evaluate kindreds with familial renal tumors for cutaneous manifestations of(More)
Junctional EB was once considered a uniformly fetal autosomal recessive skin disease. One of the first and best characterized forms of generalized JEB that has a more favorable prognosis was GABEB. Since its initial description in 1976, many additional cases have been compiled, all sharing the features of chronic blistering from birth, nail dystrophy, hair(More)
Leishmania major promastigotes were grown to late-log phase and washed and resuspended in an isosmotic buffer. When osmolality was suddenly decreased by 50%, the cells rapidly became shorter and increased in width. Cell volume, calculated assuming a prolate-ellipsoidal shape, increased 1.4 times after 1 min. Over the next several minutes, the average length(More)
The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected(More)
BACKGROUND Patients with tuberous sclerosis complex (TSC) are predisposed to developing ungual fibromas and other acral lesions. OBJECTIVE We sought to determine the numbers, types, and locations of acral skin lesions in TSC. METHODS We examined and photographed 76 adult women with TSC. RESULTS The age of the patients ranged from 20 to 69 years, with(More)
Generalized atrophic benign epidermolysis bullosa is an autosomal recessive subepidermal blistering disease typified by null mutations in COL17A1. In 1 large kindred, affected individuals were homozygous for a 2-bp deletion in COL17A1, 4003delTC, which resulted in a downstream premature termination codon, nonsense-mediated mRNA decay, and abrogation of type(More)
Lymphangioleiomyomatosis (LAM) is a multisystem disorder of women, characterized by cystic degeneration of the lungs, renal angiomyolipomas (AML), and lymphatic abnormalities. LAM lesions result from the proliferation of benign-appearing, smooth muscle-like LAM cells, which are characterized by loss of heterozygosity (LOH) of one of the tuberous sclerosis(More)
BACKGROUND Lymphangioleiomyomatosis (LAM), sporadic or in women with tuberous sclerosis complex (TSC), is characterized by cystic lung destruction, lymphatic involvement (eg, chylous pleural effusions, lymphangioleiomyomas), and renal angiomyolipomas (AMLs). The multisystem manifestations of LAM appear to result from metastatic dissemination of LAM cells(More)