AUTHOR=Stajkovska Aleksandra , Mehandziska Sanja , Stavrevska Margarita , Jakovleva Kristina , Nikchevska Natasha , Mitrev Zan , Kungulovski Ivan , Zafiroski Gjorgje , Tasic Velibor , Kungulovski Goran TITLE=Trio Clinical Exome Sequencing in a Patient With Multicentric Carpotarsal Osteolysis Syndrome: First Case Report in the Balkans JOURNAL=Frontiers in Genetics VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00113 DOI=10.3389/fgene.2018.00113 ISSN=1664-8021 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.