Abstract
Mulibrey nanism (MUscle-LIver-BRain-EYe nanism, MIM 253250) is an autosomal recessive disorder with severe prenatal-onset growth failure and multi-organ manifestations including cardiovascular, hepatic, endocrine, skeletal and opthalmologic abnormalities (Perheentupa et al, 1973; Lipsanen-Nyman, 1986; Lapunzina et al., 1995). Mulibrey nanism occurs worldwide, and some 100 patients have been identified of whom more than 80 are Finnish. Mutations in the TRIM37 gene (previously designated MUL) underlie mulibrey nanism (Avela et al., 2000). The TRIM37 gene product localizes to peroxisomes in cultured cells, which suggests that mulibrey nanism can be classified as a novel peroxisomal disorder (Kallijärvi et al., 2002). The fact that mulibrey nanism shares symptoms with known peroxisomal disorders supports the molecular evidence. Here, we discuss the clinical features of the disorder, as well as the current knowledge on the TRIM37 gene, its mutations and the protein it encodes.
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Avela, K., Lipsanen-Nyman, M., Idänheimo, N., Seemanova, E., Rosengren, S., Mäkelä, T.P., Perheentupa, J., de la Chapelle, A., and Lehesjoki, A.-E., 2000, Gene encoding a new RING-B-box-coiled-coil protein is mutated in mulibrey nanism. Nat. Genet. 25:298–301.
Borden, K.L.B., 2000, RING domains: Master builders of molecular scaffolds? J. Mol. Biol. 295:1103–112.
Cainarca, S., Messali, S., Ballabio, A., Meroni, G., 1999, Functional characterization of the Opitz syndrome gene product (midin): evidence for homodimerization and association with microtubules throughout the cell cycle. Hum. Mol. Genet.8:1387–1396.
Freemont, P.S., 2000, RING for destruction? Curr. Biol. 10(2):R84–87.
Jackson, P.K., Eldridge, A.G., Freed, E., Furstenthal, L., Hsu, J.Y., Kaiser, B.K., Reimann, J.D.. 2000, The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases. Trends. Cell. Biol. 10(10):429–39.
Kallijärvi, J., Avela, K., Lipsanen-Nyman, M., Ulmanen, I., Lehesjoki, A.-E., 2002, The TRIM37 gene encodes a peroxisomal RING-B-Box-Coiled-Coil protein: Classification of mulibrey nanism as a new peroxisomal disorder. Am. J. Hum. Genet. 70:1215–1228.
Leys, D., Petit, H., Bonte-Adnet, C, Millaire, A., Fourrier, F., Dubois, F., Rosseaux, M., Ducloux, G., 1989, Refsum’s disease revealed by cardiac disorders. Lancet 1:621.
Lipsanen-Nyman, M., 1986, Mulibrey-nanismi.Thesis,University of Helsinki
Lipsanen-Nyman, M., Perheentupa, J., Rapola, J., Sovijärvi, A., Kupari, M., 2003, Mulibrey heart disease: Clinical manifestations, long term course and pathology in a series of 48 patients born before 1985. Circulation In press.
Lapunzina, P., Rodriguez, J.I., de Matteo, E., Gracia, R., Moreno, F., 1995. Mulibrey nanism: three additional patients and a review of 39 patients. Am. J. Med. Genet. 55:349–355.
Lehesjoki, A.-E., Reed, V.A., Gardiner, R.M., Greene, N.D.E., 2001, Expression of MUL, a gene encoding a novel RBCC family ring-finger protein, in human and mouse embryogenesis. Mech. Develop. 108:221–225.
Nagase, T., Ishikawa, K., Suyama, M., Kikuno, R., Hirosawa, M., Miyajima, N., Tanaka, A., Kotani, H., Nomura, N., Ohara, O., 1998, Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res . 5:355–64.
Perheentupa, J., Autio, S., Leisti, S., Raitta, C, Tuuteri, L., 1973, Mulibrey nanism, an autosomal recessive syndrome with pericardial constriction. Lancet 2:351–355
Pickart, C.M., 2001, Mechanism underlying ubiquitination. Annu. Rev. Biochem. 70:503–33.
Reymond, A., Meroni, G., Fantozzi, A., Merla, G., Cairo, S., Luzi, L., Riganelli, D., Zanaria, E., Messali, S., Cainarca, S., Guffanti, A., Minucci, S., Pelicci, P.G., Ballabio, A., 2001, The tripartite motif family identifies cell compartments. EMBO. J. 20:2140–2151.
Sacksteder, K.A., Gould, S.J., 2000, The genetics of peroxisome biogenesis. Ann. Rev. Genet. 34:623–652.
Saurin, A.J., Borden, K.L.B., Boddy, M.N., Freemont, P.S., 1996, Does this have a familiar RING? Trends. Biochem. Sci. 21:208–214.
Schutgens, R.B.H., Ryynänen, M., Wanders, R.J.A., 1994, Peroxisomal functions in mulibrey nanism. J. Inker. Metab. Dis. 17:626.
Seemanova, E., Bartsch, O., 1999, Mulibrey nanism and Wilms tumor. Am. J. Med. Genet. 85:76–78.
Simila, S., Timonen, M., Heikkinen, E., 1980, A case of Mulibrey nanism with associated Wilms’ tumor. Clin. Genet. 17:29–30.
The French FMF consortium, 1997, A candidate gene for familial Mediterranean fever. Nat. Genet. 17:25–31.
Trockenbacher, A., Suckow, V., Foerster, J., Winter, J., Krauss, S., Ropers, H-H., Schneider, R., and Schweiger, S., 2001, MIDI, mutated in Opitz symdrome encodes an ubiquitin ligase that targets phosphatase 2A for degradation. Nat. Genet. 29:287–294.
Wajant, H., Henkler, F., Scheurich, P., 2001, The TNF-receptor-associated factor family. Scaffold molecules for cytokine receptors, kinases and their regulators. Cell. Signal. 13:389–400.
Zapata, J.M., Pawlowski, K., Haas, E.C., Ware, F., Godzik, A., Reed, J.C., 2001, A diverse family of proteins containing TRAF domains. J. Biol. Chem. 276:24242–24252.
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KallijÄrvi, J., Lehesjoki, AE., Lipsanen-Nyman, M. (2003). Mulibrey Nanism - a Novel Peroxisomal Disorder. In: Roels, F., Baes, M., De Bie, S. (eds) Peroxisomal Disorders and Regulation of Genes. Advances in Experimental Medicine and Biology, vol 544. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9072-3_3
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DOI: https://doi.org/10.1007/978-1-4419-9072-3_3
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