PDF(Pubmed)
Abstract：
Exome sequencing can interrogate thousands of genes simultaneously and it is becoming a first line diagnostic tool in genomic medicine. Herein, we applied trio clinical exome sequencing (CES) in a patient presenting with undiagnosed skeletal disorder, minor facial abnormalities, and kidney hypoplasia; her parents were asymptomatic. 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 MCTO in the Balkans.
摘要：
外显子组测序可以同时询问数千个基因，它正在成为基因组医学的一线诊断工具。在这里，我们在一名患有未确诊骨骼疾病的患者中应用了三重临床外显子组测序（CES），轻微的面部异常,和肾脏发育不全；她的父母无症状。测试先证者和她的父母导致鉴定出从头突变c.188C>T（p。Pro63Leu）在MAFB基因中，已知可导致多心角质层骨溶解综合征（MCTO）。c.188C>T突变位于MAFB的反式激活域内的热点氨基酸片段中，它是RANKL诱导的破骨细胞生成的负调节因子。MCTO是一种极为罕见的常染色体显性遗传（AD）疾病，通常是自发出现并导致腕骨骨溶解，常伴有肾病。据我们所知,这是巴尔干地区首次报道基因诊断为MCTO的研究。
