A novel mutation in TNFRSF11A gene causes pediatric osteopetrosis: case report

Osteopetrosis is a rare inherited bone disorder affected individual by osteoclast disfunction and increasing bone density. Surgery was taken for histological examination of the specimen and evidence of malignancy was not found. Finally, X-ray and gene detection lead to the diagnosis.

We report a 10-year-old girl with two years history of pus rhinorrhea, nasal obstruction and smelly nose. She was diagnosed and treated as sinusitis. But the symptoms were recurrent. Ten months ago, she was afflicted with persistent swelling and broken skin on the right cheek. All the laboratory findings showed normal. During surgery, we resected the right gingiva, the right nasal mucosa and the right facial tissue for biopsies. Histological examination showed proliferation of granulation tissue in chronic inflammatory mucosa. X-rays showed generalized sclerosis. Genetic analysis strongly supported a novel mutation of TNFRSF11A gene which caused osteoporosis. We found a novel mutation of the c.1196C > G (p.S399X) in exon 9 of TNFRSF11A. The TNFRSF11A gene encodes RANK, which is fundamental for osteoclast formation.

Osteopetrosis is a rare genetic bone disease characterized by increased bone density because of bone resorption failure. Diagnosis is based on X-ray and gene analyze. Osteoclasts are bone-related cells derived from hematopoietic cell lines. Since osteoclasts arise from a hematopoietic progenitor cell of the monocytic lineage, the defect can be corrected by hematopoietic stem cell transplantation (HSCT). Better understanding of this pathological situation and pathogenesis is so important to plan appropriate immunotherapy to benefit.