title: Wilms' tumor and novel TRIM37 mutations in an Australian patient with mulibrey nanism.
abstract: Mulibrey nanism is a rare autosomal recessive growth disorder with prenatal onset, including occasional progressive cardiopathy, characteristic facial features, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor. Mulibrey nanism is prevalent in the Finnish population and appears extremely rare elsewhere. However, cases outside of Finland may be underdiagnosed or misdiagnosed as having the 3-M or Silver-Russell syndrome, two important differential diagnostic disorders. Here, we report the first Australian patient with mulibrey nanism, in whom the occurrence of Wilms' tumor suggested the correct diagnosis. This was confirmed by the identification of two novel mutations in tripartite motif protein 37 (TRIM37) encoding a RING finger ubiquitin E3 ligase. Both mutations, the p.Cys109Ser B-box missense mutation and the p.Glu271_Ser287del in-frame deletion in the tumor necrosis factor receptor associated factor (TRAF) domain alter the subcellular localization of TRIM37. As both the B-box and the TRAF domains are predicted to be important for mediating the protein-protein interactions, these mutations may help the understanding of the cellular interactions of TRIM37. Our findings imply the importance of early molecular diagnostics in cases of suspected mulibrey nanism and of identifying novel mutations with potential relevance for unraveling the underlying molecular pathology. Ultrasound surveillance for Wilms' tumor is recommended for children with mulibrey nanism.
authors.affiliation: Folkhälsan Institute of Genetics, Department of Medical Genetics and Neuroscience Center, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland. riikka.h.hamalainen@helsinki.fi
authors.forename: R H
authors.initials: RH
authors.lastname: Hämäläinen
authors.forename: D
authors.initials: D
authors.lastname: Mowat
authors.forename: M T
authors.initials: MT
authors.lastname: Gabbett
authors.forename: T A
authors.initials: TA
authors.lastname: O'brien
authors.forename: J
authors.initials: J
authors.lastname: Kallijärvi
authors.forename: A-E
authors.initials: AE
authors.lastname: Lehesjoki
mesh_terms: D001315:Australia; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics*; D050336:Mulibrey Nanism / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D044465:White People; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D017931:DNA Primers; D009687:Nuclear Proteins; D000070584:Tripartite Motif Proteins; C411745:TRIM37 protein, human; D044767:Ubiquitin-Protein Ligases