{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:24:29Z","timestamp":1789691069027,"version":"4.0.1"},"reference-count":53,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2011,3,9]]},"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The RET\/GDNF signalling pathway plays a crucial role during development of the kidneys and the enteric nervous system. In humans, <jats:italic>RET<\/jats:italic> activating mutations cause multiple endocrine neoplasia, whereas inactivating mutations are responsible for Hirschsprung disease. <jats:italic>RET<\/jats:italic> mutations have also been reported in fetuses with renal agenesis, based on analysis of a small series of samples.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective and methods<\/jats:title>\n                  <jats:p>To characterise better the involvement of <jats:italic>RET<\/jats:italic> and <jats:italic>GDNF<\/jats:italic> in kidney development defects, a series of 105 fetuses with bilateral defects, including renal agenesis, severe hypodysplasia or multicystic dysplastic kidney, was studied. <jats:italic>RET<\/jats:italic> and <jats:italic>GDNF<\/jats:italic> coding sequences, evolutionary conserved non-coding regions (ECRs) in promoters, 3\u2032UTRs, and <jats:italic>RET<\/jats:italic> intron 1 were analysed. Copy number variations at these loci were also investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The study identified: (1) a low frequency (&lt;7%) of potential mutations in the <jats:italic>RET<\/jats:italic> coding sequence, with inheritance from the healthy father for four of them; (2) no <jats:italic>GDNF<\/jats:italic> mutation; (3) similar allele frequencies in patients and controls for most single nucleotide polymorphism variants, except for <jats:italic>RET<\/jats:italic> intron 1 variant rs2506012 that was significantly more frequent in affected fetuses than in controls (6% vs 2%, p=0.01); (4) distribution of the few rare <jats:italic>RET<\/jats:italic> variants unidentified in controls into the various 5\u2032-ECRs; (5) absence of copy number variations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These results suggest that genomic alteration of <jats:italic>RET<\/jats:italic> or <jats:italic>GDNF<\/jats:italic> is not a major mechanism leading to renal agenesis and other severe kidney development defects. Analysis of a larger series of patients will be necessary to validate the association of the <jats:italic>RET<\/jats:italic> intron 1 variant rs2506012 with renal development defects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmg.2010.088526","type":"journal-article","created":{"date-parts":[[2011,4,14]],"date-time":"2011-04-14T00:22:43Z","timestamp":1302740563000},"page":"497-504","source":"Crossref","is-referenced-by-count":61,"title":["<i>RET<\/i> and <i>GDNF<\/i> mutations are rare in fetuses with renal agenesis or other severe kidney development 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