Abstract
BACKGROUND: Skeletal dysplasia (SD) represents a series of highly heterogeneous congenital genetic diseases affecting the human skeletal system. Refined genetic diagnosis is helpful for the accurate diagnosis and prognosis evaluation of SDs. MATERIALS AND METHODS: In this study, we recruited 26 cases of SD and analyzed them with a designed sequential genetic detection. Chromosome karyotyping, microarray analysis (CMA), and whole exome sequencing (WES) techniques are performed as needed. Sanger sequencing and fluorescent quantitative PCR (QF-PCR) were used as validation methods. RESULTS: A total of 16 cases (61.5%, 16/26) received positive results at various levels of testing, including one trisomy 18, four copy number variations (CNVs), and 11 sequence variations. Additionally, four novel SD-related sequence mutations were detected in this study. CONCLUSION: Our findings provide conclusive evidence for genetic counseling of corresponding families and expand the mutation spectrum of SD. In addition, this study demonstrates that a strategy sequentially including various genetic techniques contributes to the diagnosis of highly heterogeneous genetic disorders such as SD.