Diagnostic exome identifies a novel PRKG2 mutation in a proband with skeletal dysplasia

Payal Kamdar,?Thenral S. Geetha,?Thomas Palocaren,?Madhavi Kandagaddala,?Praveen Kumar Chinniah,?Sakthivel Murugan,?Ramprasad Vedam,?Sumita Danda

About 4 years back, a case of rare disease was referred to us for genetic testing, it was a case of skeletal abnormality with Dwarfism. We couldn't find anything significant that could help the family, a year later same case was referred from CMC, Vellore, while we couldn't find anything significant in this however our senior analysts did some extensive analysis, more exploratory beyond regular analysis and found an interesting loss of function mutation in a gene. There was no direct evidence to show that it is the cause of the disease in the young girl. Interestingly, we found a published PNAS paper that showed some details on a type of dwarf cattle called American Angus cattle. Dwarfism was the major genetic defect in U.S. beef cattle. Aggressive culling was used to minimize its prevalence; however, this couldn't eliminate the recessive genetic defect. That group identified a loss of function mutation in the same gene where we found the mutation in the patient (cGMP-dependent type II protein kinase (PRKG2). A rare natural animal model studied by veterinarians gives clues to the root cause of the disease in India. Isn't it interesting to see that Biology never goes wrong! Great collaboration with Dr. Sumita, Dr. Payal and clinical experts at CMC, Vellore. Exemplary work by our colleagues Thenral, Sandhya and others at MedGenome. However, in many such cases it becomes difficult to find answers. It is gratifying to find out the answer for this family. Attached is the publication we finally published!

View the Research Paper here - https://diagnostics.medgenome.com/diagnostic-exome.pdf