TRPV4-associated skeletal dysplasias include: FDAB, ADBO, SMDK, SEDM, MD and Parastremmatic dysplasia. In this study, we recruited 3 families with congenital scoliosis and 1 family with localized digital osteopetrosis. We collected their clinical data and use the next-generation sequencing system, Sanger sequencing and RT-PCR to obtain the genetic diagnosis. Proband 1, 2, 3 all presented with early-onset kyphoscoliosis and short stature. X-ray showed platyspondyly, hemivertebra, accompanied by metaphyseal abnormalities. P1 also presented with waddling gait, bilateral streblomicrodactyly, P2 with bended upper arm and genu valgum, P3 with left femoral head subluxation. Bone turnover markers were normal. P4 presenteed with right phalanges thickening after frostbite. P4 and her mother also presented with shortening of the toes and teeth loss. X-ray showed cortical bone thickening. Two mutations of TRPV4 have been identified: Proband 1, 2, 3 were all heterozygous for c.1781G>A, a hot-spot mutation of SMDK. Proband 4 and her mother were heterozygous for a novel splice-site mutation c.1491+1G>A, and was proved to lead to skipping of exon 8 in the transcript. We firstly reported the SMDK and FDAB cases in the Chinese population. The three SMDK families carrying the same missense mutation R594H implicated that R594H may be a hot-spot mutation in Chinese. The novel splice-site mutation found in the FDAB family, is the first reported splice-site mutation of TRPV4 gene.
14 May 2016 - 17 May 2016