Mental retardation is a disorder that affects the lives of many individuals and their families worldwide. The underlying causes are heterogeneous and despite efforts to reveal them, the aetiology remains unknown for 50% of cases. Estimates of the prevalence of MR have varied between one and three percent in different studies, because of differences in definition, classification and approach to ascertainment. Most studies show that MR is about 30% more prevalent in males than females suggesting that XLMR is an important contributor to MR. Previous studies estimated that XLMR has a prevalence of 1.83 males (Herbst et al., 1980). The aim of the thesis was the ascertainment, diagnostic evaluation and gene mapping of South Australian families with possible XLMR. The South Australian Clinical Genetics Service's database (Kintrak) identified 33 families with possible XLMR of unknown cause. The clinical features and diagnostic evaluation of these families were documented. Six of these families were large enough for linkage mapping but only 2 of them agreed to participate in the current study. For one family the gene was localised between markers DXS8067 and DXS1062. Two candidate genes within the linkage interval, PHF6 and GRIA3 were screened for a mutation but no pathological mutation was found. The linkage mapping of the second family is still in progress. One of the 33 families was suspected to have Borjeson-Forssman-Lehmann syndrome and was screened for PHF6 but no mutation was found. Tarpey et al. (2007) identified protein truncating mutations in UPF3B in some patients with Lujan Fryns Syndrome (XLMR with Marfanoid body build). Therefore, the South Australian Clinical Genetics Service's database (Kintrak) was searched for males with a diagnosis of MR and Marfanoid body build and 14 individuals were found. They were screened for mutations in UPF3B gene but no pathological mutation was found. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1364228 / Thesis (M.Clin.Sc.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2009