{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:25:41Z","timestamp":1753921541430},"reference-count":32,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2006,10,13]],"date-time":"2006-10-13T00:00:00Z","timestamp":1160697600000},"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":[[2006,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Smith\u2013Magenis syndrome (SMS) is a multiple congenital anomalies\/mental retardation disorder characterized by distinct craniofacial features and neurobehavioral abnormalities usually associated with an interstitial deletion in 17p11.2. Heterozygous point mutations in the retinoic acid induced 1 gene (<jats:italic>RAI1<\/jats:italic>) have been reported in nine SMS patients without a deletion detectable by fluorescent in situ hybridization (FISH), implicating <jats:italic>RAI1<\/jats:italic> haploinsufficiency as the cause of the major clinical features in SMS. All of the reported point mutations are unique and de novo. <jats:italic>RAI1<\/jats:italic> contains a polymorphic CAG repeat and encodes a plant homeo domain (PHD) zinc finger\u2010containing transcriptional regulator. We report a novel <jats:italic>RAI1<\/jats:italic> frameshift mutation, c.3103delC, in a non\u2010deletion patient with many SMS features. The deletion of a single cytosine occurs in a heptameric C\u2010tract (CCCCCCC), the longest mononucleotide repeat in the <jats:italic>RAI1<\/jats:italic> coding region. Interestingly, we had previously reported a frameshift mutation, c.3103insC, in the same mononucleotide repeat. Furthermore, all five single base frameshift mutations preferentially occurred in polyC but not polyG tracts. We also investigated the distribution of the polymorphic CAG repeats in both the normal population and the SMS patients as one potential molecular mechanism for variability of clinical expression. In this limited data set, there was no significant association between the length of CAG repeats and the SMS phenotype. However, we identified a 5\u2010year\u2010old girl with an apparent SMS phenotype who was a compound heterozygote for an <jats:italic>RAI1<\/jats:italic> missense mutation inherited from her father and a polyglutamine repeat of 18 copies, representing the largest known CAG repeat in this gene, inherited from her mother. \u00a9 2006 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31510","type":"journal-article","created":{"date-parts":[[2006,10,14]],"date-time":"2006-10-14T21:25:52Z","timestamp":1160861152000},"page":"2454-2463","source":"Crossref","is-referenced-by-count":42,"title":["<i>RAI1<\/i> point mutations, CAG repeat variation, and SNP analysis in non\u2010deletion Smith\u2013Magenis syndrome"],"prefix":"10.1002","volume":"140A","author":[{"given":"Weimin","family":"Bi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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