Novel X-linked mental retardation syndrome with short stature maps to Xq24

We describe a large family from Sardinia, Italy, in which a novel X- linked mental retardation (XLMR) syndrome segregates. The phenotype observed in t he 8 affected males includes severe mental retardation (MR), lack of speech , coarse face, distinctive skeletal features with short stature, brachy. da ctyly of fingers and toes, small downslanting palpebral fissures, large bul bous nose, hypoplastic ear lobe and macrostomia. Carrier females are not me ntally retarded, although some of them have mild dysmorphic features such a s minor ear lobe abnormalities, as well as language and learning problems. Linkage analysis for X- chromosome markers resulted in a maximum lod score of 3.61 with marker DXS1001 in Xq24. Recombination observed with flanking m arkers identified a region of 16 cM for further study. None of the other XL MR syndromes known to map in the same region shows the same composite pheno type. This evidence strongly suggests that the genetic disease in this fami ly is unique. (C) 2001 Wiley-Liss, Inc.