Hamartin and tuberin function as a complex which is involved in the control of cell growth and cell division. The complex appears to interact with RHEB GTPase, thus sequestering it from activating mTOR signalling, part of the growth factor (insulin) signalling pathway. Thus, mutations at the<unk> 1 and<unk> 2 loci result in a loss of control of cell growth and cell division, and therefore a predisposition to forming tumors.<unk>  affects tissues from different germ layers. Cutaneous and visceral lesions may occur, including angiofibroma, cardiac rhabdomyomas, and renal angiomyolipomas. The central nervous system lesions seen in this disorder include hamartomas of the cortex, hamartomas of the ventricular walls, and subependymal giant cell tumors, which typically develop in the vicinity of the foramina of Monro. Molecular genetic studies have defined at least two loci for<unk> . In<unk> 1, the abnormality is localized on chromosome 9q34, but the nature of the gene protein, called hamartin, remains unclear. No missense mutations occur in<unk> 1. In<unk> 2, the gene abnormalities are on chromosome 16p13. This gene encodes tuberin, a guanosine triphosphatase–activating protein. The specific function of this protein is unknown. In<unk> 2, all types of mutations have been reported; new mutations occur frequently. Few differences have yet been observed in the clinical phenotypes of patients with mutation of one gene or the other. Cells from individuals with pathogenic mutations in the<unk> 2 gene display abnormal accumulation of glycogen that is associated with depletion of lysosomes and autophagic impairment. The defective degradation of glycogen by the autophagy-lysosome pathway is, at least in part, independent of impaired regulation of mTORC1 and is restored, in cultured cells, by the combined use of PKB/Akt and mTORC1 pharmacological inhibitors.
Tuberous sclerosis
Sugarman syndrome
Krabbe disease
Neurofibromatosis
Neurofibromatosis type 4
Neurofibromatosis type I
Neurofibromatosis type II
Leschke syndrome