Novel PCNT Mutation underlies MOPD II With The Smallest Teeth

Objective: To report two Thai children affected with Microcephalic Osteodysplastic Primordial Dwarfism (MOPD) type II. MOPD Type II is an extremely rare autosomal recessive disorder. Methods: Clinical examination and mutation analysis of PCNT were performed. Results: Clinical findings consist of IUGR, microcephaly, prominent nose, small pinnae, very short stature, slender long bones, abnormal pelvis, cafe-au-lait spots, acanthosis nigricans, and hypo-and hyperpigmented skin. Acanthosis nigricans found in our patients was most likely related to insulin-resistant diabetes. High-pitched voice was noted. The striking feature was the extremely small permanent teeth. The permanent teeth were much smaller than the primary ones. Alveolar bone was severely hypoplastic. Teeth were malformed and single-rooted or rootless. The girl had a supernumerary maxillary permanent molar. Mutation analysis of the 47 exons of the PCNT gene reveals p.E148X homozygous mutation in the affected children and heterozygous mutation in the parents. PCNT encodes the centrosome protein pericentrin that localizes specifically to centrosomes throughout the cell cycle. Absence of PCNT results in disorganized mitotic spindles, loss of centrosome, missegregation of chromosomes, and followed by cell death. Stroke secondary to cerebral vascular anomalies is a common cause of early death. The smallest human ever been recorded was affected with MOPD II. She was a sexually mature 12-year-old girl, who was 20 inches tall and weighed 5 pounds. The Late Pleistocene hominid fossils (the Hobbit) from the island of Flores, Indonesia were postulated to be the remains of those who were affected with MOPD II. Conclusion: We report a novel homozygous p.E148X mutation in the PCNT gene in a Thai family affected with MOPD II with the smallest teeth ever been reported in the literature. Interestingly the loss-of-function mutation found in our patients has created an extra tooth in the affected girl. (This research was supported by The Thailand Research Fund)