RESUMEN
Osteogenesis imperfecta (OI) is a group of clinically and genetically heterogeneous disorders characterized by decreased bone mass and recurrent bone fractures. Transmembrane protein 38B (TMEM38B) gene encodes trimeric intracellular cation channel type B (TRIC-B), mutations of which will lead to the rare form of autosomal recessive OI. Here we detected pathogenic gene mutations in TMEM38B and investigated its phenotypes in three children with OI from two non-consanguineous families of Chinese Han origin. The patients suffered from recurrent fractures, low bone mass, mild bone deformities and growth retardation, but did not have impaired hearing or dentinogenesis imperfecta. Next-generation sequencing and Sanger sequencing revealed a homozygous novel acceptor splice site variant (c.455-7T>G in intron 3, p.R151_G152insVL) in family 1 and a homozygous novel nonsense variant (c.507G>A in exon 4, p.W169X) in family 2. The parents of the probands were all heterozygous carriers of these mutations. We reported the phenotype and novel mutations in TMEM38B of OI for the first time in Chinese population. Our findings of the novel mutations in TMEM38B expand the pathogenic spectrum of OI and strengthen the role of TRIC-B in the pathogenesis of OI.