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Novel mutations in the TRIM37 gene in Mulibrey Nanism
Author(s) -
Hämäläinen Riikka H.,
Avela Kristiina,
Lambert Julie A.,
Kallijärvi Jukka,
Eyaid Wafaa,
Gronau Jürgen,
Ignaszewski Andrew P.,
McFadden Deborah,
Sorge Giovanni,
LipsanenNyman Marita,
Lehesjoki AnnaElina
Publication year - 2004
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.9233
Subject(s) - missense mutation , biology , exon , genetics , gene , mutation , mutant , ring finger , dwarfism
Abstract Mulibrey nanism is an autosomal recessive prenatal‐onset growth disorder of unknown pathogenesis. The main clinical features are pre‐ and postnatal growth failure, characteristic dysmorphic craniofacial features, heart disease, and hepatomegaly. Five truncating mutations in the TRIM37 gene have previously been reported in Mulibrey nanism patients. The TRIM37 protein encodes a novel protein of unknown function. It contains a tripartite motif (TRIM, also denoted the RING‐B‐box‐Coiled‐coil or RBCC domain) and a TRAF (tumor necrosis factor‐receptor associated factor) domain. TRIM37 localizes to peroxisomes classifying Mulibrey nanism as a peroxisomal disorder. Here we have characterized the genomic structure of the TRIM37 gene, which has 24 exons spanning& tilde;109 kb of genomic DNA. Further, we report six novel disease‐associated mutations, five of which predict a truncated protein: c.745C>T (p.Gln249X), c.1411C>T (p.Arg471X), c.2056C>T (p.Arg686X), and an 8.6 kb genomic deletion (c.1314+507_1668‐207del resulting in p.Arg439fsX4). The sixth mutation (c.965G>T) is the first missense mutation (p.Gly322Val) associated with Mulibrey nanism. It affects the TRAF domain of TRIM37 and results in altered subcellular localization of the mutant TRIM37 protein, further suggesting that it is pathogenic. © 2004 Wiley‐Liss, Inc.