Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
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Question: Mowat-Wilson syndrome is a genetic condition characterized by a recognizable facial phenotype in addition to moderate to severe cognitive disability with severe speech impairment and variable multiple congenital anomalies. The anomalies may include Hirschsprung disease, heart defects, structural eye anomalies including microphthalmia, agenesis of the corpus callosum, and urogenital anomalies. Microcephaly, seizure disorder and constipation are common. All typical cases result from haploinsufficiency of the ZEB2 (also known as ZFHX1B or SIP-1) gene, with over 100 distinct mutations now described. Approximately 80% of patients have a nonsense or frameshift mutation detectable by sequencing, with the rest having gross deletions necessitating a dosage sensitive assay. Here we report on the results of comprehensive molecular testing for 27 patients testing positive for MWS. Twenty-one patients had a nonsense, frameshift, or splice site mutation identified by sequencing; 14 of which localized to exon 8 and 17 of which are novel. Six patients had deletions in the ZEB2 gene, including two novel partial gene deletions. This report, the first such analysis in North American patients, adds to the growing list of both novel pathogenic mutations associated with MWS, as well as other variants in the ZEB2 gene. In addition, we suggest an economical testing strategy.

Answer: Which gene is responsible for the development of the Mowat-Wilson syndrome?


Question: Patients with multiple myeloma (MM) experience pathologic fractures, bone pain, hypercalcemia, neurologic symptoms, and renal insufficiency with substantial morbidity and mortality. Bisphosphonates have been used successfully for the management of MM-related bone disease. Increased incidence of osteonecrosis of the jaw has been observed in patients with cancer receiving bisphosphonate therapy. Recent advances in the pathobiology of MM-related bone disease and other cancer-related bone metastases have led to the identification of novel therapeutic targets, such as receptor activator of nuclear factor-kappaB (RANK); its ligand (RANKL); and a decoy receptor, osteoprotegerin, for the development of potential targeted agents. Initials studies have demonstrated that targeting RANK/ RANKL signaling with the fully human monoclonal antibody denosumab prevented skeletal complications in patients with MM and other cancers with bone metastases. Ongoing studies evaluating the clinical utility of denosumab in cancer- related bone destruction have been discussed. In addition, several potential targets, such as macrophage inflammatory protein-1alpha, chemokine receptors 1 and 5, interleukin-3, and Wnt signaling, are b riefly described.

Answer: To the ligand of which receptors does Denosumab (Prolia) bind?


Question: Rotterdam Centrum is bounded by the emplacement of the Rotterdam Centraal railway station and the Goudsesingel in the North, the Tunneltraverse of the Henegouwerlaan and 's-Gravendijkwal in the West, the Nieuwe Maas River in the South and the Oostplein in the East.

Answer:
Which is the body of water by Rotterdam Centrum?