Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H

Valentina Saccone, Michela Palmieri, Luigia Passamano, Giulio Piluso, Germana Meroni, Luisa Politano, Vincenzo Nigro

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

TRIM32 belongs to a large family of proteins characterized by a tripartite motif, possibly involved in the ubiquitination process, acting as an E3 ligase. In addition, TRIM32 has six NHL repeats with putative interaction properties. A homozygous mutation at the third NHL repeat (D487N) has been found in patients with limb girdle muscular dystrophy 2H (LGMD2H). This mutation was only identified in the inbred Manitoba Hutterite or their descendants. Interestingly, a mutation in the B-box domain of TRIM32 cosegregates with Bardet-Biedl syndrome type 11 (BBS11). The signs of BBS11 include obesity, pigmentary and retinal malformations, diabetes, polydactyly, and no muscular dystrophy, suggesting an alternative disease mechanism. We aim to ascertain whether D487N is the only pathological LGMD2H allele, limited to Hutterites. We studied the TRIM32 gene in 310 LGMD patients with no mutations at the other known loci. We identified four patients with novel mutated alleles. Two mutations were homozygous and missing in controls. These mutations also clustered at the NHL domain, suggesting that a specific (interaction) property might be abolished in LGMD2H patients. No mutations were found at the B-box region where the BBS11 mutation is found. We tested TRIM32 and its mutants by yeast-two-hybrid assay, developing an interaction test to validate mutations. All LGMD2H mutants, but not the BBS11, lost their ability to self-interact. The interaction of TRIM32 mutants with E2N, a protein involved in the ubiquitination process, was similarly impaired. In conclusion, the mutations here reported may cause muscular dystrophy by affecting the interaction properties of TRIM32.

Original languageEnglish
Pages (from-to)240-247
Number of pages8
JournalHuman Mutation
Volume29
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Mutation
Muscular Dystrophies
Ubiquitination
Alleles
Limb-girdle muscular dystrophy type 2H
Manitoba
Polydactyly
Two-Hybrid System Techniques
Ubiquitin-Protein Ligases
Proteins
Obesity
Bardet-Biedl Syndrome 11
Genes

Keywords

  • LGMD2H
  • Muscular dystrophies
  • TRIM32
  • Yeast two-hybrid

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Saccone, V., Palmieri, M., Passamano, L., Piluso, G., Meroni, G., Politano, L., & Nigro, V. (2008). Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. Human Mutation, 29(2), 240-247. https://doi.org/10.1002/humu.20633

Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. / Saccone, Valentina; Palmieri, Michela; Passamano, Luigia; Piluso, Giulio; Meroni, Germana; Politano, Luisa; Nigro, Vincenzo.

In: Human Mutation, Vol. 29, No. 2, 02.2008, p. 240-247.

Research output: Contribution to journalArticle

Saccone, V, Palmieri, M, Passamano, L, Piluso, G, Meroni, G, Politano, L & Nigro, V 2008, 'Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H', Human Mutation, vol. 29, no. 2, pp. 240-247. https://doi.org/10.1002/humu.20633
Saccone, Valentina ; Palmieri, Michela ; Passamano, Luigia ; Piluso, Giulio ; Meroni, Germana ; Politano, Luisa ; Nigro, Vincenzo. / Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2H. In: Human Mutation. 2008 ; Vol. 29, No. 2. pp. 240-247.
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