The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD, Australia.
Am J Hum Genet. 2012 Mar 9;90(3):494-501. doi: 10.1016/j.ajhg.2012.01.003. Epub 2012 Mar 1.
Multicentric carpotarsal osteolysis (MCTO) is a rare skeletal dysplasia characterized by aggressive osteolysis, particularly affecting the carpal and tarsal bones, and is frequently associated with progressive renal failure. Using exome capture and next-generation sequencing in five unrelated simplex cases of MCTO, we identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. A further six unrelated simplex cases with MCTO were also heterozygous for previously unreported mutations within this same region, as were affected members of two families with autosomal-dominant MCTO. MAFB encodes a transcription factor that negatively regulates RANKL-induced osteoclastogenesis and is essential for normal renal development. Identification of this gene paves the way for development of novel therapeutic approaches for this crippling disease and provides insight into normal bone and kidney development.
多发性中心性掌跖骨溶解症（MCTO）是一种罕见的骨骼发育不良，其特征为侵袭性骨质溶解，特别影响腕骨和跗骨，常伴有进行性肾功能衰竭。我们对 5 例无关联的单纯性 MCTO 病例进行了外显子捕获和下一代测序，在 MAFB 的单一外显子的 51 个碱基对区域内发现了以前未报道的错义突变，通过 Sanger 测序进行了验证。另外 6 例无关联的单纯性 MCTO 病例也携带同一区域内以前未报道的突变，常染色体显性 MCTO 的受累成员也是如此。MAFB 编码一种转录因子，可负调控 RANKL 诱导的破骨细胞生成，对正常肾脏发育至关重要。该基因的鉴定为这种致残疾病的新型治疗方法的开发铺平了道路，并为正常骨骼和肾脏发育提供了深入了解。
