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In this study we report on a novel X\u2010linked recessive, congenital syndrome in a family with developmental delay and SNHL that maps to a locus associated with mental retardation (MR) for which no causative gene has been identified. The X\u2010linked recessive inheritance and congenital nature of the syndrome was confirmed by detailed clinical investigation and the family history. Linkage mapping of the X\u2010chromosome was conducted to ascertain the disease locus and candidate genes were screened by direct sequencing and STRP analysis. The recessive syndrome was mapped to Xp11.3\u2013q21.32 and a deletion was identified in a regulatory region upstream of the <jats:italic>POU3F4<\/jats:italic> gene in affected family members. Since mutations in <jats:italic>POU3F4<\/jats:italic> cause deafness at the DFN3 locus, the deletion is the likely cause of the SNHL in this family. The choroideremia (<jats:italic>CHM<\/jats:italic>) gene was also screened and a novel missense change was identified. The alteration changes the serine residue at position 89 in the Rab escort 1 protein (REP\u20101) to a cysteine (S89C). Prenylation of Rab proteins was investigated in patients and the location of REP\u20101 expression in the brain determined. However, subsequent analysis revealed that this change in <jats:italic>CHM<\/jats:italic> was polymorphic having no effect on REP\u20101 function. Although the causative gene at the MR locus in this family has not been identified, there are a number of genes involved in syndromic and nonsyndromic forms of MR that are potential candidates. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.31995","type":"journal-article","created":{"date-parts":[[2007,10,12]],"date-time":"2007-10-12T23:47:18Z","timestamp":1192232838000},"page":"2564-2575","source":"Crossref","is-referenced-by-count":16,"title":["Molecular characterization of a novel X\u2010linked syndrome involving developmental delay and deafness"],"prefix":"10.1002","volume":"143A","author":[{"given":"Michael S.","family":"Hildebrand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle G.","family":"de Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiong 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