{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:13:21Z","timestamp":1758399201607},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T00:00:00Z","timestamp":1437436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label \/><jats:p>Three systems with VACTERL association findings\u2010 mutations of the Sonic Hedgehog (SHH) signaling pathway in mice, murine adriamycin teratogenicity, and human Fanconi anemia (FA) pathway mutations, may all involve a similar mechanism. SHH is up\u2010regulated in irradiated cells, and DNA breaks common with radiation damage in the adriamycin and FA systems are plausible signals for such effects, which would affect development. Since FA related DNA breakage occurs throughout life, SHH disturbances may account for later FA related findings involving hematopoietic and malignancy issues. In support, androgen, a standard treatment for FA hematologic failure, down\u2010regulates SHH, and common FA malignancies such as squamous cell carcinomas and acute myeloid leukemia have been linked to enhanced SHH function. This suggests that interventions lowering SHH levels may be useful therapeutically. Also supporting a connection between pre\u2010 and post\u2010 natal findings, the frequency and number of VACTERL anomalies with FA correlate with the severity and onset of hematopoietic and malignancy issues. In FA, radial anomalies are the most common of these defects, followed by renal findings, while vertebral and gastrointestinal anomalies are relatively uncommon, a pattern that differs from observations of the VACTERL association. Genes with more severe effects also show a greatly increased incidence of brain abnormalities, and a paucity of such findings with other FA genes suggests that brain development is relatively refractory to SHH related effects, accounting for the rarity of such findings with the association. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37257","type":"journal-article","created":{"date-parts":[[2015,7,21]],"date-time":"2015-07-21T12:36:49Z","timestamp":1437482209000},"page":"2594-2598","source":"Crossref","is-referenced-by-count":7,"title":["<i>Sonic Hedgehog<\/i>, VACTERL, and Fanconi anemia: Pathogenetic connections and therapeutic implications"],"prefix":"10.1002","volume":"167","author":[{"given":"Mark","family":"Lubinsky","sequence":"first","affiliation":[{"name":"6003 W. 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