title: Putative modifier genes in mevalonate kinase deficiency.
abstract: 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.
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Marcuzzi
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Vozzi
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Girardelli
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste I‑34128, Italy.
authors.forename: Paola Maura
authors.initials: PM
authors.lastname: Tricarico
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Knowles
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.affiliation: Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste I‑34128, Italy.
authors.forename: Josef
authors.initials: J
authors.lastname: Vuch
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tommasini
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Piscianz
authors.affiliation: Department of Advanced Diagnostic and Clinical Trials, Institute for Maternal and Child Health‑IRCCS 'Burlo Garofolo', Trieste I‑34137, Italy.
authors.forename: Anna Monica
authors.initials: AM
authors.lastname: Bianco
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005091:Exons; D005260:Female; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D054078:Mevalonate Kinase Deficiency / Q000235:genetics* / Q000473:pathology; D008798:Mevalonic Acid / Q000652:urine; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D051981:Uracil-DNA Glycosidase / Q000235:genetics
chemical_list: D008565:Membrane Proteins; C486770:PEX11G protein, human; D051981:Uracil-DNA Glycosidase; D008798:Mevalonic Acid