[PIK3CA mutation analysis in isolated macrodactyly]

Objective: To systematically investigate PIK3CA mutations in isolated macrodactyly. Methods: Overgrowth tissues from 12 isolated macrodactyly patients who were treated at Department of Hand Surgery, Beijing Jishuitan Hospital from May to August 2017 were collected during operation.There were 6 male and 6 female patients with average age of 4.5 years. DNA was tested for PIK3CA mutation using a targeted Sanger DNA sequencing method.Samples with negative Sanger result were tested with a next generation DNA sequencing(NGS)panel targeting 47 cancer hotspot genes including PIK3CA. Results: By targeted Sanger sequencing, PIK3CA mutations were detected in 9 of the 12 patients, with mutation level ranging from 7% to 27%.The PIK3CA mutations observed were p. His1047Arg, p.His1047Leu, p.Glu545Lys, and p. Glu542Lys.NGS found p. Glu453Lys in one additional patient, allowing the total positive rate to 10/12.All PIK3CA mutations detected in the study were cancer hotspot mutations.Among all tissue types tested, adipose tissue had the highest mutation detection rate(9/9), followed by nerve(10/12) and skin(10/12). Conclusions: A high proportion of isolated macrodactyly patients carry a PIK3CA mutation.Adipose, nerve, and skin are ideal tissue resources for PIK3CA mutation detection.Targeted Sanger sequencing with reflex to NGS represents a cost-effective strategy to test PIK3CA mutations in isolated macrodactyly.