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PRS designates the locus for a syndromal form of X-linked mental retardation (Prieto syndrome) characterized by minor facial anomalies, ear malformation, abnormal growth of teeth, clinodactyly, sacral dimple, patellar luxation, malformation of lower limbs, abnormalities of the fundus of the eye, and subcortical cerebral atrophy [Prieto et al., 19871. Linkage analysis localized the disease locus between DXS84 (Xp21.1) and DXS255 [Xp11.22; Watty et al., 19911. Here we present additional linkage data that provide further support and refinement of this localization. Individual 111-18 gave birth to a male (IV-1 in Fig. l), currently aged 2Y12 years, who clearly shows delayed psychomotor development. He began to walk at 23 months and his speech is delayed. In addition, he shows the characteristic facial anomalies, "dysplastic" ears, sacral dimple, and clinodactyly, as do all other affected males in this family.
For the linkage analysis, the inclusion of IV-1 results in 3 additional informative meioses. Furthermore, 4 additional markers were typed in this family: DXS1068 [Gyapay et al., 19941, DXS7 [Moore et al., 19921, MAO-A [Hendriks et al., 19921, and SYNIAFtAFl [Kirchgessner et al., 19913. Data of the extended linkage study using the markers known to be linked to PRS confirm the former localization with a maximum multipoint LOD score of 3.58 in the middle of the OTC-MAO-A interval. As IV-1 inherited the OTC-allele of his maternal grandfather, and 11-1 inherited the diseaseassociated haplotype for SYNIARAF and MAO-A, these findings allow a refined localization of the PRS between OTC and MAO-A, reducing the localisation to a 9 cM interval [Fain et al., 19951. Further studies with markers mapped in the interval OTC-MAOA may lead to a more precise localization of the disease locus, which would be an important step towards the identification of the genels involved in the disease. In any case, the present refined localisation supposes a great improvement in accuracy for future prenatal diagnoses.