The causes of CDG in many patients are undiscovered.
The aim i s to develop a novel method to identify CDG mutations that are not solved by traditional methods. There are three specific aims: 1. Establish which CDG cell lines are poorly transduced by Adeno-associated virus (AAV) AAV4 and 5. 2. Complement those CDG cells with a cDNA library, identify complemented cells by AAV, and sequence the complementing cDNA. 3. Identify mutations in CDG cells and correct abnormal glycosylation with normal cDNA.
Aim 1 is to determine which CDG cells are suitable for complemetation. Only those cells that are not efficiently transduced by viral vectors AAV4 and AAV5 can be used by this method.
Aim 2 &3 identify the causes of CDG. Four steps are needed. First, CDG cells are transduced by a human liver retroviral cDNA library. Second, the rescued cells are identified by AAV transduction. Third, complemented cDNAs are identified by RT-PCR and mutations in patients are identified by sequencing. The last step is correcting abnormal glycosylation by complementing patient's cells with the specific wild type genes. The long-term goals are to discover new types of CDG and understand the relationship among mutations, glycosylation and pathology.
| Sun, Liangwu; Zhao, Yingjun; Zhou, Kun et al. (2013) Insufficient ER-stress response causes selective mouse cerebellar granule cell degeneration resembling that seen in congenital disorders of glycosylation. Mol Brain 6:52 |
| Kranz, Christian; Basinger, Alice A; Gucsavas-Calikoglu, Muge et al. (2007) Expanding spectrum of congenital disorder of glycosylation Ig (CDG-Ig): sibs with a unique skeletal dysplasia, hypogammaglobulinemia, cardiomyopathy, genital malformations, and early lethality. Am J Med Genet A 143A:1371-8 |
| Kranz, Christian; Ng, Bobby G; Sun, Liangwu et al. (2007) COG8 deficiency causes new congenital disorder of glycosylation type IIh. Hum Mol Genet 16:731-41 |
| Kranz, Christian; Sun, Liangwu; Eklund, Erik A et al. (2007) CDG-Id in two siblings with partially different phenotypes. Am J Med Genet A 143A:1414-20 |
