Key result
Novel TRIM37 mutations expand the genetic spectrum of Mulibrey nanism with six new variants identified.
Why the study?
Mulibrey nanism is a prenatal-onset growth disorder with unknown pathogenesis and limited knowledge of TRIM37 gene mutations.
Observational
Identification of six novel mutations in the TRIM37 gene expands the genetic spectrum of Mulibrey nanism and highlights the functional importance of the TRAF domain.
Answers are grounded in this paper and cite their sources.
May aid molecular diagnosis of Mulibrey nanism; extends TRIM37 spectrum but leaves functional validation open.
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 approximately 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.
No takes yet. Share an insight, caveat, or question.
Hämäläinen et al. (2004) conducted an observational in Mulibrey nanism. TRIM37 gene mutations was evaluated on Identification of novel mutations and genomic structure characterization. Six novel disease-associated mutations in the TRIM37 gene were identified in Mulibrey nanism, including five truncating mutations and one missense mutation affecting the TRAF domain.
Synapse has enriched 10 related papers. Consider them for comparative context: