Abstract:

Objective To study 4 cases of acrodysostosis 1 caused by PRKAR1A gene mutation based on their clinical manifestations and laboratory parameters. Methods Clinical data and laboratory testing results of 4 cases of acrodysostosis 1 were collected,and whole exome high-throughput sequencing was performed. Phenotype-driven variant filters were performed to identify candidate variants,and Sanger sequencing was used to verify the parental origin of the variants. The pathogenicity of genetic variation was classified according to Standards and Guidelines for the Interpretation of Sequence Variants. Results The main clinical manifestations of the 4 cases were short stature（-3s - -6s）,low weight（-2s - -4s）,brachydactyly,dysmorphic facial features and multi-hormone resistance. Different clinical manifestations were observed among individuals,and some patients had partial growth hormone deficiency. Pathogenic mutations in PRKAR1A were detected in the 4 cases. Of them,3 cases had the mutation c.1102C>T/p.Arg368*,and the one had the mutation c.1118A>G/p.Tyr373Cys. Conclusion Totally,2 new mutations in PRKAR1A have been detected,and there is heterogeneity in the clinical manifestations of patients with acrodysostosis 1.

Key words: PRKAR1A gene, Acrodysostosis type 1, Whole exome high-throughput sequencing