{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:55:47Z","timestamp":1782809747745,"version":"3.54.5"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2008,4,15]],"date-time":"2008-04-15T00:00:00Z","timestamp":1208217600000},"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":[[2008,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have investigated the breakpoints of a balanced reciprocal translocation between chromosomes X and 5, [46,X,t(X;5)(p11.1;q31.1)], in a woman with mild mental retardation (MR). Methylation studies showed a 100% skewed X\u2010inactivation in patient\u2010derived lymphocytes. Cloning and sequencing of the junction fragment from the X derivative showed that the breakpoint occurred in intron 3 of the <jats:italic>CDKL3<\/jats:italic> gene on chromosome 5 and in a region devoid of genes on chromosome X. Quantitative RT\u2010PCR analyses on patient\u2010derived lymphoblastoid cells documented a significant 50% decrease of the <jats:italic>CDKL3<\/jats:italic> transcript level. Allelic expression analysis, using an intronic SNP that was RT\u2010PCR amplified from <jats:italic>CDKL3<\/jats:italic> pre\u2010mRNA, provided further evidence that the <jats:italic>CDKL3<\/jats:italic> gene was transcribed from only one allele. Decreased <jats:italic>CDKL3<\/jats:italic> gene expression was definitively confirmed at the protein level by immunoblot analysis. <jats:italic>CDKL3<\/jats:italic> is a member of a subset of the cdc2\u2010related protein kinase family that shows similarity to both mitogen\u2010activated protein kinases (MAPK) and cyclin\u2010dependant kinases (cdks). Importantly, one member of the family, <jats:italic>CDKL5<\/jats:italic>, has been implicated in atypical Rett syndrome, West syndrome, and X\u2010linked infantile spasm, all including MR as a manifestation. Expression studies demonstrated that the mouse homologue, <jats:italic>mCdkl3<\/jats:italic>, was expressed in all brain regions investigated and throughout mouse development, a pattern that is consistent with a role in development and brain function. Together the data suggest that haploinsufficiency of <jats:italic>CDKL3<\/jats:italic> in the t(X;5) patient contributes to her phenotype, and that the <jats:italic>CDKL3<\/jats:italic> gene is a strong candidate for nonsyndromal autosomal dominant MR. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32274","type":"journal-article","created":{"date-parts":[[2008,4,15]],"date-time":"2008-04-15T16:47:18Z","timestamp":1208278038000},"page":"1267-1279","source":"Crossref","is-referenced-by-count":20,"title":["Inactivation of the <i>CDKL3<\/i> gene at 5q31.1 by a balanced t(X;5) translocation associated with nonspecific mild mental 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