Putative modifier genes in mevalonate kinase deficiency

Annalisa Marcuzzi, Diego Vozzi, Martina Girardelli, Paola Tricarico Maura, Alessandra Knowles, Sergio Crovella, Josef Vuch, Alberto Tommasini, Elisa Piscianz, Anna Monica Bianco

Research output: Contribution to journalArticlepeer-review


Mevalonate kinase deficiency (MKD) is an autosomal recessive auto-inflammatory disease, caused by impairment of the mevalonate pathway. Although the molecular mechanism remains to be elucidated, there is clinical evidence suggesting that other regulatory genes may be involved in determining the phenotype. The identification of novel target genes may explain non-homogeneous genotype-phenotype correlations, and provide evidence in support of the hypothesis that novel regulatory genes predispose or amplify deregulation of the mevalonate pathway in this orphan disease. In the present study, DNA samples were obtained from five patients with MKD, which were then analyzed using whole exome sequencing. A missense variation in the PEX11γ gene was observed in homozygosis in P2, possibly correlating with visual blurring. The UNG rare gene variant was detected in homozygosis in P5, without correlating with a specific clinical phenotype. A number of other variants were found in the five analyzed DNA samples from the MKD patients, however no correlation with the phenotype was established. The results of the presents study suggested that further analysis, using next generation sequencing approaches, is required on a larger sample size of patients with MKD, who share the same MVK mutations and exhibit 'extreme' clinical phenotypes. As MVK mutations may be associated with MKD, the identification of specific modifier genes may assist in providing an earlier diagnosis.

Original languageEnglish
Pages (from-to)3181-3189
Number of pages9
JournalMolecular Medicine Reports
Issue number4
Publication statusPublished - Apr 1 2016


  • Correlation genotype-phenotype
  • Gene
  • Mevalonate kinase deficiency
  • Orphan disease
  • Whole exome sequencing

ASJC Scopus subject areas

  • Biochemistry
  • Cancer Research
  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Oncology


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