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Context Maturity-onset diabetes of the young type 5 (MODY5) is caused by mutations of the hepatocyte nuclear factor 1 homeobox β gene (HNF1B). Although clinical characteristics and therapeutic management of MODY5 are increasingly better defined, adequate consideration of the frequent association of MODY5 with 17q12 deletion syndrome is often missing. Evidence Acquisition We report two cases of patients with 17q12 deletion syndrome who presented to our clinic. Furthermore, we reviewed the existing literature to improve systematic diagnostic and therapeutic approaches. A PubMed search using the terms 17q12 deletion syndrome, diabetes mellitus type MODY5, and/or HNF1B was performed. Evidence Synthesis Three hundred sixty-one cases of postnatal 17q12 deletion syndrome were assessed, and details on clinical manifestations, diagnostic approaches, and therapeutic management were reviewed and compared with the two cases at our clinic. Furthermore, data on pathogenic mechanisms and their clinical implications were evaluated. Conclusion The 17q12 deletion syndrome usually comprises MODY5, structural or functional abnormalities of the kidneys, and neurodevelopmental or neuropsychiatric disorders. A complete deletion of HNF1B can be found in about 50% of patients with MODY5. A wide variety of additional clinical features, including genital and brain malformations, has been reported. Because HNF1B deletions are virtually always part of a 17q12 deletion syndrome and common genetic analyses for evaluation of MODY5 are unable to detect the deletion of a 1.4-Mb chromosomal region, initial attention to the syndromal features at the stage of diagnosis is of considerable importance for establishing correct diagnosis, subsequent therapy, and interdisciplinary patient care.

We show here that Mg 2+ acquisition by CorA is essential for Helicobacter pylori in vitro, as corA mutants did not grow in media without Mg 2+ supplementation. Complementation analysis performed with an Escherichia coli corA mutant revealed that H. pylori CorA transports nickel and cobalt in addition to Mg 2+ . However, Mg 2+ is the dominant CorA substrate, as the corA mutation affected neither cobalt and nickel resistance nor nickel induction of urease in H. pylori . The drastic Mg 2+ requirement (20 mM) of H. pylori corA mutants indicates that CorA plays a key role in the adaptation to the low-Mg 2+ conditions predominant in the gastric environment.

The reactivity of the essential element iron necessitates a concerted expression of ferritins, which mediate iron storage in a nonreactive state. Here we have further established the role of the Helicobacter pylori ferritin Pfr in iron metabolism and gastric colonization. Iron stored in Pfr enabled H. pylori to multiply under severe iron starvation and protected the bacteria from acid-amplified iron toxicity, as inactivation of the pfr gene restricted growth of H. pylori under these conditions. The lowered total iron content in the pfr mutant, which is probably caused by decreased iron uptake rates, was also reflected by an increased resistance to superoxide stress. Iron induction of Pfr synthesis was clearly diminished in an H. pylori feoB mutant, which lacked high-affinity ferrous iron transport, confirming that Pfr expression is mediated by changes in the cytoplasmic iron pool and not by extracellular iron. This is well in agreement with the recent discovery that iron induces Pfr synthesis by abolishing Fur-mediated repression of pfr transcription, which was further confirmed here by the observation that iron inhibited the in vitro binding of recombinant H. pylori Fur to the pfr promoter region. The functions of H. pylori Pfr in iron metabolism are essential for survival in the gastric mucosa, as the pfr mutant was unable to colonize in a Mongolian gerbil-based animal model. In summary, the pfr phenotypes observed give new insights into prokaryotic ferritin functions and indicate that iron storage and homeostasis are of extraordinary importance for H. pylori to survive in its hostile natural environment.