New GAA mutations in Japanese patients with GSDII (Pompe disease).

Glycogen storage disease type II (Pompe disease) is inherited by autosomal recessive transmission and caused by a deficiency of acid alpha-glucosidase (GAA), resulting in impaired degradation and lysosomal accumulation of glycogen. The GAA gene, responsible for this disease, has been mapped to chromosome 17q25.2-25.3. To date, more than 70 disease-causing mutations have been identified. In this study, we present four mutations found in three Japanese patients with the juvenile form of glycogen storage disease type II; three of these mutations were new (R224W, S619R, and R660H). The pathogenicity of these new mutations was verified by the loss of function of the mutant enzymes expressed in COS cells.

Novel TSC1 and TSC2 mutations in Japanese patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome characterized by development of unusual tumor-like growths. Involvement of the brain is associated with the most problematic clinical manifestations of TSC, including intellectual retardation, epilepsy and abnormal behaviors. Until now, over 300 mutations of TSC1 and TSC2 were reported. Here, we report one novel mutation of TSC1 (Q897X) and five novel mutations of TSC2 (c.336+1 G>A, L345R, E700K, R905G, K914K) identified in Japanese patients with TSC. We also identified three new polymorphisms in TSC2 (N331N, A431A, S802G). The TSC1 mutation was predicted to cause a nonsense substitution whereas all of the five TSC2 mutations were predicted to cause either a splicing error or a missense substitution. In accordance with previous findings, the patients with TSC1 mutations had milder clinical manifestations than those with TSC2 mutations.