Abstract
The lamin B receptor (LBR) gene is located in chromosome 1q42.12 and encodes the lamin B receptor, an intracellular protein that binds to lamin B. LBR mutations are associated with a broad phenotypic spectrum ranging from non-lethal to lethal skeletal dysplasias. The typical phenotypes include the Pelger-Huet anomaly (PHA) and embryonic lethal Greenberg dysplasia (GRBGD). With the further study of this gene, other phenotypes have been found in different individuals. This retrospective study analyzed recurrent prenatal moderate skeletal dysplasias in Chinese fetuses. Nothing malformed was detected in the fetal karyotype and microarray, while the whole-exome sequencing identified a homozygous variant (NM_002296.4:c.1757G>A, NP_002287.2:p.Arg586His) in exon 14 of the LBR gene in both fetuses. Mutation analysis in the parents confirmed that the c.1757G>A variation is heterozygous by Sanger sequencing. Intensive analysis on bioinformatics and familial co-segregation suggest that the homozygous variation in the LBR gene is responsible for this recurrent prenatal moderate skeletal dysplasia. Moreover, moderate skeletal dysplasias differ from typical GRBGD phenotypes. Our findings are based on the DNA base test and the prenatal diagnosis of skeletal dysplasia, which can be helpful in proper phenotyping and contribute to a better understanding of the correlation between the phenotype and genotype.