Mapping to distal Xq28 of nonspecific X-linked mental retardation MRX72: Linkage analysis and clinical findings in a three-generation Sardinian family

Families with mentally retarded males found to be negative for FRAXA and FR AXE mutations are useful in understanding the genetic basis of X-linked men tal retardation. According to the most recent data (updated to 1999), 69 MR X loci have been mapped and 6 genes cloned. Here we report on a linkage stu dy performed on 20 subjects from a ti-generation Sardinian family segregati ng a non-specific X-linked recessive mental retardation (XLMR)(MRX72) assoc iated with global delay of all psychomotor development. Five of 8 affected males have been tested for mental age, verbal and performance skills and be havioral anomalies; mental impairment ranged from mild to severe. Only mino r anomalies were present in the affected subjects. Two-point linkage analys is based on 28 informative microsatellites spanning the whole X chromosome demonstrated linkage between the disorder and markers DXS1073 and F8c in Xq 28 (maximum Lod score of 2.71 at theta = 0.00). Multipoint linkage analysis confirmed the linkage with a Z(max) of 3.0 at theta = 0.00 at DXS1073 and F8c. Recombination in an affected male at DXS1073 and F8c allowed us to del imit centromerically and telomerically the region containing the putative c andidate gene. The region, where MRX72 maps, overlaps that of another MRX f amilies previously mapped to Xq28, two of which harbored mutations in GDI. Involvement of this gene was excluded in our family, suggesting another MRX might reside in Xq28. Am. J. Med. Genet. 94:376-382, 2000. (C) 2000 Wiley- Liss, Inc.