@article {8315,
	title = {Putative modifier genes in mevalonate kinase deficiency.},
	journal = {Mol Med Rep},
	volume = {13},
	year = {2016},
	month = {2016 Apr},
	pages = {3181-9},
	abstract = {<p>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 {\textquoteright}extreme{\textquoteright} clinical phenotypes. As MVK mutations may be associated with MKD, the identification of specific modifier genes may assist in providing an earlier diagnosis.</p>},
	issn = {1791-3004},
	doi = {10.3892/mmr.2016.4918},
	author = {Marcuzzi, Annalisa and Vozzi, Diego and Girardelli, Martina and Tricarico, Paola Maura and Knowles, Alessandra and Crovella, Sergio and Vuch, Josef and Tommasini, Alberto and Piscianz, Elisa and Bianco, Anna Monica}
}
@article {8075,
	title = {Patients{\textquoteright} Induced Pluripotent Stem Cells to Model Drug Induced Adverse Events: A Role in Predicting Thiopurine Induced Pancreatitis?},
	journal = {Curr Drug Metab},
	volume = {17},
	year = {2015},
	month = {2015},
	pages = {91-8},
	abstract = {<p>Induced pluripotent stem cells (iPSC) can be produced from adult cells by transfecting them with a definite set of pluripotency-associated genes. Under adequate growth conditions and stimulation iPSC can differentiate to almost every somatic lineage in the body. Patients{\textquoteright} derived iPSC are an innovative model to study mechanisms of adverse drug reactions in individual patients and in cell types that cannot be easily obtained from human subjects. Proof-of concept studies with known toxicants have been performed for liver, cardiovascular and central nervous system cells: neurons obtained from iPSC have been used to elucidate the mechanism of chemotherapy-induced peripheral neuropathy by evaluating the effects of neurotoxic drugs such as vincristine. However, no study has been performed yet on pancreatic tissue and drug induced pancreatitis. Thiopurines (azathioprine and mercaptopurine) are immunosuppressive antimetabolite drugs, commonly used to treat Crohn{\textquoteright}s disease. About 5\% of Crohn{\textquoteright}s disease patients treated with thiopurines develop pancreatitis, a severe idiosyncratic adverse event; these patients have to stop thiopurine administration and may require medical treatment, with significant personal and social costs. Molecular mechanism of thiopurine induced pancreatitis (TIP) is currently unknown and no fully validated biomarker is available to assist clinicians in preventing this adverse event. Hence, in this review we have reflected upon the probable research applications of exocrine pancreatic cells generated from patient specific iPS cells. Such pancreatic cells can provide excellent insights into the molecular mechanism of TIP. In particular three hypotheses on the mechanism of TIP could be explored: drug biotransformation, innate immunity and adaptative immunity.</p>},
	issn = {1875-5453},
	author = {Stocco, Gabriele and Lanzi, Gaetana and Yue, Fengming and Giliani, Silvia and Sasaki, Katsunori and Tommasini, Alberto and Pelin, Marco and Martelossi, Stefano and Ventura, Alessandro and Decorti, Giuliana}
}
