Mother and daughter with 45,X/46,X,r(X)(p22.3q28) and mental retardation: Analysis of the x‐inactivation patterns

We report on a mother and daughter both with a 45,X/46,X,r(X)(p22.3q28) karyotype and mental retardation. Fluorescence in situ hybridization (FISH) and microsatellite analyses for 14 loci/region at Xp22.3 and seven loci/region at Xq28 indicated that the ring X chromosome was missing a roughly 12‐Mb region from Xp22.3 with the breakpoint between DXS85 and DXS9972, and another region of less than 100 kb from Xq28 with the breakpoint distal to the region defined by the FISH probe c8.2/1. X‐inactivation analysis, using the methylation status of the AR gene (exon 1) as an indicator, showed that the normal and ring X chromosomes in the X,r(X)(p22.3q28) cell lineage were randomly inactivated. The Xp22.3 deleted region partially overlaps with the regional intervals of MRX19, MRX21, MRX24, MRX37, MRX43, and MRX49 associated with heterozygote manifestation. Therefore, it is likely that one or more of these MRX genes, subject to X‐inactivation, are lost from the ring X chromosome, and that reduced expression of the MRX gene(s) caused by random X‐inactivation has resulted in mental retardation in the mother and daughter. Am. J. Med. Genet. 91:267–272, 2000. © 2000 Wiley‐Liss, Inc.