A Family of LBR Biallelic Pathogenic Variants Resulting in Rhizomelic Skeletal Dysplasia with Pelger-Huët Anomaly.

INTRODUCTION

The lamin-B receptor (LBR) gene has two primary functions: maintaining the structural integrity of the nuclear envelope and playing a role in cholesterol biosynthesis. Heterozygous variants in the LBR gene have been associated with Pelger-Huët anomaly (PHA, OMIM #169400), while homozygous or compound heterozygous mutations have been associated with rhizomelic skeletal dysplasia, with or without PHA (OMIM #618019) and Greenberg dysplasia (OMIM #215140).

CASE PRESENTATION: We report a 4-year-old boy presenting with short stature and short limbs and his mother exhibiting milder findings. Genetic analysis revealed a heterozygous c.1640A>G (p.Asn547Ser) and c.43C>T (p.Arg15*) variants in the LBR gene in both the boy and his mother. The father was identified as a heterozygous carrier of the c.43C>T (p.Arg15*) variant. Peripheral blood smears confirmed the PHA in the patient and his parents.

CONCLUSION

The phenotypic differences observed between the mother and male child in our study highlight the genetic variability and regressive nature of LBR-related skeletal dysplasias. This report shows the complexity of LBR-related phenotypes and expands the clinical spectrum of LBR mutations in rhizomelic skeletal dysplasia with PHA.