Calcification of joints and arteries: Second report with novel NT5E mutations and expansion of the phenotype

Abstract

Calcification of joints and arteries (CALJA; MIM 211800) is an extremely rare mendelian disorder of isolated calcification that is characterized by late onset calcification of the extremity arteries and hand and foot joint capsules. Mutations of NT5E, encoding cluster of differentiation 73, have been implicated in CALJA. Here we report on a Chinese family with CALJA and novel compound heterozygous mutations (c.1360G>A (p.Gly454Arg) and c.1387C>T (p.Arg463X)) in NT5E. Our study represents the second report on patients with CALJA associated with NT5E mutations. The clinical features expand the previously reported phenotype of NT5E mutations. The propositus has calcification of the lower extremity arteries and hand and foot joint capsules similar to those previously reported patients. However, he also has calcification of the upper extremity arteries. By protein structural modeling, we found the mutation p.Gly454Arg may disrupt the folding of β-pleated sheet and destabilize the protein structure. Our findings will provide clues to the phenotype-genotype relations and may assist not only in the clinical diagnosis but also in the interpretation of genetic information used for prenatal diagnosis and genetic counseling.