Stajkovska Aleksandra, Mehandziska Sanja, Stavrevska Margarita, Jakovleva Kristina, Nikchevska Natasha, Mitrev Zan, Kungulovski Ivan, Zafiroski Gjorgje, Tasic Velibor, Kungulovski Goran
Bio Engineering LLC, Skopje, Macedonia.
Zan Mitrev Clinic, Skopje, Macedonia.
Front Genet. 2018 Apr 5;9:113. doi: 10.3389/fgene.2018.00113. eCollection 2018.
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 mutation c.188C>T (p.Pro63Leu) in the 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.
外显子组测序能够同时检测数千个基因，正成为基因组医学中的一线诊断工具。在此，我们对一名患有未确诊骨骼疾病、轻微面部异常和肾发育不全的患者应用了三联体临床外显子组测序（CES）；她的父母没有症状。对先证者及其父母进行检测后，在该基因中鉴定出一个c.188C>T（p.Pro63Leu）突变，已知该突变会导致多中心腕跗骨溶解综合征（MCTO）。c.188C>T突变位于MAFB转录激活域内的一个热点氨基酸区域，MAFB是RANKL诱导破骨细胞生成的负调节因子。MCTO是一种极其罕见的常染色体显性（AD）疾病，通常自发出现，会导致腕跗骨溶解，常伴有肾病。据我们所知，这是巴尔干地区首例关于基因诊断MCTO的研究报告。
