{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:39:34Z","timestamp":1791322774180,"version":"4.3.1"},"reference-count":100,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,9,2]],"date-time":"2005-09-02T00:00:00Z","timestamp":1125619200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2005,10]]},"abstract":"<jats:p>Holoprosencephaly (HPE) is a genetically heterogeneous developmental field defect in which midline cleavage of the forebrain and craniofacial structures is impaired. Based on the analysis of HPE patients with chromosome rearrangements, at least six loci for the disorder have been assigned. The sonic hedgehog gene (<jats:italic>SHH<\/jats:italic>) at 7q36 has been identified as the <jats:italic>HPE3<\/jats:italic> locus. Cleidocranial dysplasia (CCD) is an autosomal dominant skeletal disorder characterized by clavicular, pelvic and dental anomalies. It is caused by mutations in the osteoblast\u2010specific transcription factor <jats:italic>CBFA1\/RUNX2<\/jats:italic>, which maps to 6p21. We report a 20\u2010year\u2010old female with premaxillary agenesis (part of the HPE spectrum), as well as skeletal abnormalities and impacted teeth reminiscent of CCD. She carries a <jats:italic>de novo<\/jats:italic> 6;7 reciprocal translocation, with breakpoints at 6p21.1 and 7q36. We have shown previously that the 7q36 breakpoint maps 15\u2003kb telomeric to the 5\u2032 end of <jats:italic>SHH<\/jats:italic>, which explains the patient's HPE phenotype. Now, using fluorescence <jats:italic>in situ<\/jats:italic> hybridization, we have identified a P1 artificial chromosome clone 800\u2003kb upstream of <jats:italic>CBFA1\/RUNX2<\/jats:italic> that spans the 6p breakpoint. We propose that the proband's complex phenotype is due to two position\u2010effect (PE) mutations, one at each translocation breakpoint, which have altered the expression of the <jats:italic>SHH<\/jats:italic> and <jats:italic>CBFA1\/RUNX2<\/jats:italic> genes. The role of PE mutations in human disease is also reviewed.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2005.00498.x","type":"journal-article","created":{"date-parts":[[2005,9,2]],"date-time":"2005-09-02T13:12:22Z","timestamp":1125666742000},"page":"349-359","source":"Crossref","is-referenced-by-count":29,"title":["Holoprosencephaly and cleidocranial dysplasia in a patient due to two position\u2010effect mutations: case report and review of the 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