A novel frameshift mutation in the TRPS1 gene caused Tricho-rhino-phalangeal syndrome type I and III in a Japanese family

Tricho-rhino-phalangeal syndrome (TRPS) is a heritable congenital syndrome characterized by craniofacial and skeletal abnormalities. TRPS is an autosomal dominant syndrome with high penetrance and wide phenotypic variability. TRPS is classified into three subtypes; TRPS types I (TRPS I; OMIM 190350) and III (TRPS III; OMIM 190351) have distinct clinical manifestations that often correspond to distinct mutations in the TRPS1 gene. Patients with either TRPS I or III have sparse scalp hair, a nose with a bulbous tip, and skeletal abnormalities including cone-shaped epiphyses at the phalanges and short stature (1). Skeletal malformations in patients with TRPS III are more severe than that in patients with TRPS I (2). TRPS type II (TRPS II; OMIM 150230) is caused by a contiguous gene deletion involving TRPS1 and EXT1. Several genotype-phenotype relationship studies on TRPS indicate that TRPS III is at the most severe end of the TRPS clinical spectrum and TRPS I is at the least severe end (3). Here, we describe a Japanese family with two TRPS cases with intra-familial phenotypic variability (TRPS I and TRPS III). Both cases were associated with a single newly described frameshift mutation in TRPS1.