Trio Clinical Exome Sequencing in a Patient with Multicentric Carpotarsal Osteolysis Syndrome: First Case Report in the Balkans

Testing the proband and her parents led to the identification of a de novo mutation c.188C>T (p.Pro63Leu) in the MAFB gene, which is known to cause multicentric carpotarsal osteolysis syndrome (MCTO). The c.188C>T mutation lies in a hotspot amino acid stretch within the transactivation domain of MAFB, which is a negative regulator of RANKL-induced osteoclastogenesis. MCTO is an extremely rare autosomal dominant (AD) disorder that typically arises spontaneously and causes carpotarsal osteolysis, often followed by nephropathy. To the best of our knowledge, this is the first study reporting genetically diagnosed multicentric carpotarsal osteolysis syndrome in the Balkans.

对先证者（proband）及其父母开展检测后，成功在MAFB基因中鉴定出一处新发突变c.188C>T（p.Pro63Leu），该突变可引发多中心腕跗骨溶解综合征（multicentric carpotarsal osteolysis syndrome, MCTO）。该c.188C>T突变位于MAFB的反式激活结构域内的热点氨基酸区段，而MAFB是核因子κB受体活化因子配体（RANKL）诱导破骨细胞生成的负调控因子。MCTO是一种极为罕见的常染色体显性（autosomal dominant, AD）遗传病，通常呈自发发生，临床表现为腕跗骨溶解，后续常继发肾病。据我们所知，本研究为巴尔干地区首次报道经遗传学确诊的多中心腕跗骨溶解综合征病例。