Infantile systemic hyalinosis associated with a putative splice-site mutation in the ANTXR2 gene

Infantile systemic hyalinosis (ISH) is a rare autosomal recessive genetic disorder characterized by dermal and subcutaneous fibromatosis, joint contractures and bone deformities. The condition usually presents at birth, resulting in death in infancy. ISH is caused by mutations in the anthrax toxin receptor 2 gene, ANTXR2, also known as CMG2. We report an Indian child with ISH in whom we identified a homozygous acceptor splice site mutation, IVS2-4G>A. In silico analysis of this sequence showed that it changed predicted cryptic splicing, leading to out-of-frame transcripts and little, if any, functional protein. Mutations in the ANTXR2 gene can also cause juvenile hyaline fibromatosis (JHF). Although there are currently no effective treatments for ISH or JHF, identification of pathogenetic mutations in the ANTXR2 gene makes DNA-based prenatal diagnosis feasible for subsequent pregnancies.