Case Report: Exome Sequencing Identified a Novel Compound Heterozygous Variation in Causing Bruck Syndrome Type 2.

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 and 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 gene with two variants, namely c.2038C>T (p.R680) and c.191_201+3 delATACTGTGAAGGTA (p.Y64Cfs12). 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 gene, provided solid evidence for the family's counseling in regard to future pregnancies, strongly supported the application of WES in prenatal diagnosis, and might give insight into the understanding of PLOD2 function.