A familial case of spondyloepiphyseal dysplasia tarda caused by a novel splice site mutation in TRAPPC2

[Introduction] Spondyloepiphyseal dysplasia tarda (SEDT: MIM # 313400) is a rare, X-linked recessive skeletal disease, characterized by disproportionately short stature with vertebral malformation. Clinical expression of SEDT begins with flattening of the growth curve before puberty. Defects in trafficking protein particle complex subunit 2 (TRAPPC2; MIM # 300202) are the only known causes of SEDT. TRAPPC2 plays an important role in transporting protein from the endoplasmic reticulum (ER) to cytoplasm. Most newly synthesized proteins leave the ER via coat protein complex II (COPII) vesicles. However, procollagen (PC) that is too large to fit into typical COPII vesicles requires larger transport carriers. It is known that TRAPPC2, acting in concert with transport and Golgi organization 1 (TANGO1), is pivotal for biogenesis of a megacarrier for large PC. This collaborative action of TANGO1 and TRAPPC2 sustains ER export of large PC, and its derangement may explain the defective chondrogenesis underlying SEDT.