title: Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly in  a Finnish woman: first confirmation of a duplication in RUNX2 as  pathogenic variant.
abstract: Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly (MDMHB) is an autosomal-dominant bone dysplasia that until now has only been reported in French Canadian individuals. We have recently identified an intragenic duplication in RUNX2, encompassing exons 3 to 5, as a cause of MDMHB in French Canadian families. Here we describe a 20-year-old Finnish woman who had typical clinical and radiological signs of MDMHB, the first reported individual with MDMHB who is not of French-Canadian origin. Copy number variant assays based on quantitative PCR of genomic DNA showed the presence of three copies within a part of RUNX2. Sequencing RUNX2 cDNA from the skin fibroblasts revealed a duplication of exons 3 to 5. The results demonstrated that the intronic breakpoints of the duplication differed from those previously found in the French Canadian family, but that the consequences on RUNX2 transcript were identical. These findings demonstrate that the MDMHB phenotype results from an intragenic duplication of RUNX2 exons 3 to 5 also outside of the community where the disorder was first identified.
authors.forename: Kristiina
authors.initials: K
authors.lastname: Avela
authors.forename: Heljä
authors.initials: H
authors.lastname: Hirvinen
authors.forename: Mouna
authors.initials: M
authors.lastname: Ben Amor
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
mesh_terms: D000015:Abnormalities, Multiple / Q000000981:diagnostic imaging* / Q000235:genetics; D059327:Brachydactyly / Q000000981:diagnostic imaging* / Q000235:genetics; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D019066:Facies; D005260:Female; D005385:Fingers / Q000002:abnormalities* / Q000000981:diagnostic imaging; D005387:Finland; D020440:Gene Duplication; D056726:Genetic Association Studies; D006801:Humans; D008437:Maxilla / Q000002:abnormalities* / Q000000981:diagnostic imaging; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging* / Q000235:genetics; D011859:Radiography; D055815:Young Adult
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human