[PIK3CA mutation analysis in isolated macrodactyly].

Area of Science:

• Genetics
• Molecular Biology
• Dermatology

Background:

• Isolated macrodactyly is a rare congenital condition characterized by localized overgrowth.
• The genetic underpinnings of isolated macrodactyly are not fully understood.
• PIK3CA mutations are implicated in various overgrowth syndromes.

Purpose of the Study:

• To systematically investigate the presence and spectrum of PIK3CA mutations in patients with isolated macrodactyly.
• To evaluate the efficacy of different sequencing methods for PIK3CA mutation detection in affected tissues.
• To identify optimal tissue types for genetic analysis in isolated macrodactyly.

Main Methods:

• DNA was extracted from overgrowth tissues of 12 isolated macrodactyly patients.
• Targeted Sanger DNA sequencing was initially employed to detect PIK3CA mutations.
• Next-generation sequencing (NGS) was used as a reflex test for samples negative by Sanger sequencing, targeting 47 cancer hotspot genes including PIK3CA.

Main Results:

• PIK3CA mutations were detected in 10 out of 12 patients (83.3%), with mutation levels ranging from 7% to 27%.
• Common PIK3CA mutations identified include p.His1047Arg, p.His1047Leu, p.Glu545Lys, and p.Glu542Lys.
• Adipose tissue (9/9), nerve (10/12), and skin (10/12) showed the highest mutation detection rates, indicating their suitability for genetic testing.

Conclusions:

• A significant proportion of isolated macrodactyly cases are associated with PIK3CA mutations.
• Adipose, nerve, and skin tissues are valuable for PIK3CA mutation detection in this condition.
• A combined approach of targeted Sanger sequencing with reflex NGS is a cost-effective strategy for diagnosing PIK3CA-related isolated macrodactyly.