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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK072890-03
Application #
7264676
Study Section
Special Emphasis Panel (ZRG1-F04B (20))
Program Officer
Hyde, James F
Project Start
2005-08-01
Project End
2008-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
3
Fiscal Year
2007
Total Cost
$58,036
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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; 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
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