Glycogen storage disease type II (GSD II) is the most severe subtype of glycogen storage disease, usually with onset in infancy, with marked cardiac hypertrophy, respiratory distress, and usually death from cardiopulmonary failure by age 2 years. Effective treatment for the disease is still lacking.

Catecholamine-sensitive polymorphic ventricular tachycardia (CPVT) is a very rare and severe hereditary heart rate disorder of the cardiac ion channel with an average age of 7-9 years and, in rare cases, autosomal recessive inheritance even in infancy. The causative genes are RYR2, CASQ2, TRDN, KCNJ2, ANK2 and CALM1, and untreated patients have a 30-50% mortality rate by age 30.

In 2019, Director Yanmin Zhang of Xi'an Children's Hospital published two consecutive articles on rare disease lineage building in children in Stem Cell Research in collaboration with Nanjing Ailp Regenerative Medicine Technology Co. Both samples were very rare double mutations, GSDII with GAA gene carrying two mutation loci, R608X and E888X [1], and CPVT with double mutations in RyR2 and SCN10A [2], both of which are the first cases of establishing iPS cell (induced Pluripotent Stem Cell) lines in China, preserving both a precious clinical resources, but also provide an ideal in vitro model for the study of rare diseases in children. Not only GSDII and CPVT, but also more rare diseases caused by genetic mutations, can be established by reprogramming techniques to establish iPS cell lines, which can later be differentiated downstream to establish disease models and applied in disease mechanism research and drug screening.

Both articles provide functional validation of iPS cell lines and demonstrate their potential for downstream use.

Paper 1

Paper 2

A. Cloning bright-field photographs
B. iPSC karyotype analysis
C. iPSC immunofluorescence
D/E. iPSC mutation site validation
F/G/H. Flow purity and stemness assays
I/J/K. Tri-embryonic trial differentiation

References

1. Yanmin Zhang. et, al. 2019. Generation of induced pluripotent stem cells (iPSCs) from an infant with Pompe disease carrying with compound mutations of R608X and E888X in GAA gene. Stem Cell Research.

2. Yanmin Zhang. et, al. 2019. Generation of induced pluripotent stem cells (iPSCs) from an infant with catecholaminergic polymorphic ventricular tachycardia carrying the double heterozygous mutations A1855D in RyR2 and Q1362H in SCN10A. Stem Cell Research.