A Case of Autosomal Dominant Osteopetrosis Type 2 with a CLCN7 Gene Mutation

Abstract

Osteopetrosis is a rare genetic disease characterized by increased bone density and bone fractures due to defective osteoclast function. Autosomal dominant osteopetrosis type 2 (ADO-2), Albers-Schonberg disease, is characterized by the sclerosis of bones, predominantly involving the spine, pelvis and the base of the skull. Here, we report a typical case of osteopetrosis in a 17.7-year-old male who carries a heterozygous c.746C>T mutation in exon 9 in the chloride voltage-gated channel 7 (CLCN7) gene. The patient’s spine showed multiple sclerotic changes including sandwich vertebra. His father had the same mutation but his skeletal radiographs were normal. This is the first reported case of ADO-2, confirmed by genetic testing in a Korean patient.

Keywords: Osteopetrosis; bone density; osteoclast; sclerosis; mutation.

Figure 1

A) X-rays of the skull showing generalized increase in bone density. The sclerosis is more prominent in the base of the skull. B) Typical end-plate thickening and sclerosis producing the classic “sandwich vertebrae” appearance. C) Sclerosis in the iliac wings, acetabuli and femur heads. However, typical “bone-within-bone” appearance cannot be noted in the patient. D) The patient’s father showed normal bone density

Figure 2

A heterozygous missense mutation was identified in the patient and his father. A heterozygous C to T transition is shown at position 746 in exon nine of CLCN7 gene, changing a proline to leucine substitution at codon position 249