Variant in PLEC Is Associated With Congenital Insensitivity to Pain

Objectives:
To investigate the molecular etiology of congenital insensitivity to pain (CIP) with underdeveloped alveolar bone.
Methods:

Clinical, radiographic examinations were performed on two sons of a consanguineous Thai family. Histological study and transmission electron micrography were performed on the skin. Whole exome and Sanger sequencing were done to identify genetic variations. Detailed histories were recorded through interviewing.
Results:



Both patients had no pain sensation since birth. Progressive corneal dystrophy led to blindness. When teeth started to erupt, they both bit their tongues and lips resulting in scar lesions and oral constriction. At times, they pulled their teeth out. Acro-osteolysis was observed. Radiographic examination showed underdeveloped alveolar bone and absence of distal phalanges of hands and feet. At the ages of 28 and 19, both patients claimed had regained pain sensation. Genetic findings showed a novel homozygous variant c.4039C>T; p.Arg1347Cys (rs372256096) in PLEC in both patients. This mutation is predicted to be disease-causing, deleterious, and probably damaging by Mutation Tasting, SIFT, and PolyPhen-2, respectively.
Conclusions: We have identified PLEC as a novel gene for congenital insensitivity to pain.