Exome sequencing as a tool for short stature gene discovery: analysis of a Korean family with pseudohypoparathyroidism

A 4 bp deletion in GNAS has known to be the causal mutation for pseudohypoparathyroidism. In this study, we performed sanger sequencing on exons of GNAS and identified the 4 bp causal deletion in Korean family with pseudohypoparathyroidism. Despite the finding of the deletion, underlying genetics of short stature in the family is unclear since paternal lineage showed history of short stature and mother didn’t show short stature. Therefore, we performed exome sequencing to explore putative causal mutations responsible for short stature phenotype in the Korean family with pseudohypoparathyroidism. Initially, we discovered 58,829 variants from four members of the family by exome sequencing. Subsequent variant filtering removed possible non-causal variants based on public databases including 1,000 genomes project and Exome Sequencing Project. After selecting dominant functional variants inherited from the father, we identified 40 putative candidates. Among them, the strongest possible candidate would be ALPL that has known to be related with hypophosphatasia. In conclusion, our results could provide additional insight into the understanding of genetics related with short stature phenotype.