Comparison of the functional and structural characteristics of rare TSC2 variants with clinical and genetic findings.

The TSC1 and TSC2 gene products interact to form the tuberous sclerosis complex (TSC), an important negative regulator of the mechanistic target of rapamycin complex 1 (TORC1). Inactivating mutations in TSC1 or TSC2 cause TSC, and the identification of a pathogenic TSC1 or TSC2 variant helps establish a diagnosis of TSC. However, it is not always clear whether TSC1 and TSC2 variants are inactivating.

Correction: Monoallelic Germline TSC1 Mutations Are Permissive for T Lymphocyte Development and Homeostasis in Tuberous Sclerosis Complex Individuals.

[This corrects the article DOI: 10.1371/journal.pone.

CNV analysis in 169 patients with bladder exstrophy-epispadias complex.

Background: The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the congenital uro-rectal malformation spectrum. Initial studies have implicated rare copy number variations (CNVs), including recurrent duplications of chromosomal region 22q11.21, in BEEC etiology.

Variants Within TSC2 Exons 25 and 31 Are Very Unlikely to Cause Clinically Diagnosable Tuberous Sclerosis.

Inactivating mutations in TSC1 and TSC2 cause tuberous sclerosis complex (TSC). The 2012 international consensus meeting on TSC diagnosis and management agreed that the identification of a pathogenic TSC1 or TSC2 variant establishes a diagnosis of TSC, even in the absence of clinical signs. However, exons 25 and 31 of TSC2 are subject to alternative splicing.

Monoallelic germline TSC1 mutations are permissive for T lymphocyte development and homeostasis in tuberous sclerosis complex individuals.

Germline and somatic biallelic mutations of the Tuberous sclerosis complex (TSC) 1 and TSC2 gene products cause TSC, an autosomal dominant multifocal hamartomatosis with variable neurological manifestations. The consequences of TSC1 or TSC2 loss in cells of hematopoietic origin have recently started to be unveiled in mice and showed to hinder the development of proper T cell immunity. To date, the consequences of germline TSC1 mutations and/or its loss in mature human T cells remain to be determined.