Bruck Syndrome (BRKS) is a rare type of recessive osteogenesis imperfecta (OI) and consists of two subtypes, BRKS1 and BRKS2, which are caused by variations in FKBP10 and PLOD2 genes, respectively. In this study, a family that had experienced multiple miscarriages and recurrent fetal skeletal dysplasia was recruited for the purpose of a multiplatform laboratory investigation. Prenatal genetic testing with whole-exome sequencing (WES) identified a compound heterozygous variation in the PLOD2 gene with two variants, namely c.2038C>T (p.R680∗) and c.191_201+3 delATACTGTGAAGGTA (p.Y64Cfs∗12). The amino acids affected by the two variants maintained conserved across species. And the result of immunohistochemistry (IHC) indicated that the expression of PLOD2 protein in the proband’s osteochondral tissue was significantly decreased. These findings in our study expanded the variation spectrum of PLOD2 gene, provided solid

Keywords: PLOD2 gene, Bruck syndrome type 2, osteogenesis imperfecta, whole-exome sequencing, immunohistochemistry detection

INTRODUCTION

Congenital skeletal dysplasia (SD) often displays severe in utero manifestations, which provides clues and challenges for prenatal diagnosis (Offiah, 2015; Liu et al., 2019). First, they can provide evidence for the timely formation of management plans; on the other hand, due to the strong clinical heterogeneity of SDs, it is difficult to accurately judge the prognosis by these indeterminate indications alone (Konstantinidou et al., 2009; Offiah, 2015). Under such circumstances, a meticulously designed strategy of genetic detection would help overcome the setbacks in clinical differential diagnosis (Zhou et al., 2018; Yang et al., 2019).