Defining the pathogenicity of creatine deficiency syndrome

Defining the pathogenicity of DNA sequence variation.

Mendelian Disorders For many cardiac or vascular conditions in which the initial presentation may be fatal, a strong genotype–phenotype correlation is of fundamental importance if genetic diagnosis or prognostication is ever to be useful. Even in classic monogenic disorders, in which large effect sizes are observed, genetic prediction is often confounded by reduced penetrance, wide variation in...

Creatine Deficiency Syndromes

Pathogenesis of creatine transporter deficiency

Defining the pathogenicity of optineurin in juvenile open-angle glaucoma.

PURPOSE Juvenile open-angle glaucoma (JOAG) differs from primary open-angle glaucoma in that it is usually a more severe phenotype and has an earlier age of onset. Optineurin was recently associated with a variant of POAG that is characterized by intraocular pressure within normal limits: normal-tension glaucoma. The present study tested whether OPTN sequence changes play a role in early-onset ...

Creatine, central nervous system and creatine deficiency syndromes

It was long thought that most of brain creatine was of peripheral origin. However, recent works have demonstrated that creatine crosses blood-brain barrier only with poor efficiency, and that CNS must ensure parts of its creatine needs by its own creatine synthesis pathway, thank to the brain expression of AGAT and GAMT (creatine synthesis) and SLC6A8 (creatine transporter). This new understand...