The A242T mutation in the low-density lipoprotein receptor-related protein 5 gene in one Chinese family with osteosclerosis.

Objective: Osteosclerosis (OMIM: 144750) is a type of autosomal dominant bone disease caused by a mutation in the low-density lipoprotein receptor-related protein 5 (LRP5) gene. The case of a Chinese family with two affected individuals is reported in the present study in order to investigate the clinical characteristics and virulence genes of this sclerosing bone disorder.

Methods: Biochemical and radiographic examinations and bone mineral density (BMD) and genetic analyses were performed in two patients and eight other family members.

Results: The 40-year-old proband (II-1) and her 64-year-old mother (I-2) both had chronic lumbodorsal pain, an elongated mandible and torus palatinus in the center of the hard palate. No fractures were observed in any of the family members. Skull, mandibular and pelvic X-rays in each of the two patients revealed thickened cranial plates, an enlarged sella turcica, an elongated mandible and cortical thickening of the long bones. The BMD values of the two patients was significantly higher than the standard age- and sex-matched adult mean reference values. Both patients had higher serum sclerostin levels, while their renal function markers and serum calcium, phosphonium, parathyroid hormone (PTH) and 25(OH)D levels were within the normal ranges. The heterozygous missense mutation p.Ala242Thr in exon 4 of the LRP5 gene was detected in the two patients, while the other family members and 200 healthy donors had normal wild-type genotypes.

Conclusion: The A242T mutation in the LRP5 gene resulted in a high bone mass phenotype with an elongated mandible and torus palatinus in this osteosclerotic family.