FRIED-SYNDROME IS A DISTINCT X-LINKED MENTAL-RETARDATION SYNDROME MAPPING TO XP22

In 1972, Fried described a large Scottish family affected by X linked mental retardation (XLMR), hydrocephalus, and mild facial dysmorphism. The phenotype has considerable similarity to the MASA syndrome, which results from mutations of the L1CAM gene in Xq28, and this family has since been assumed to be an example of this condition. We have reinve stigated the family for Linkage to X chromosome markers, and obtained additional clinical information on surviving affected subjects. The ph enotype in these patients has evolved into a distinctive syndrome, wit h severe mental retardation (MR), spastic diplegia, ventricular dilata tion, and calcification of the basal ganglia. Linkage to Xq28 markers has been excluded, suggesting that Fried syndrome is not allelic with MASA syndrome. Two point and multipoint linkage analysis indicates tha t the gene for this condition lies within the interval KAL-DXS989 in X p22. We propose the designation Fried syndrome to emphasise the disord er's distinctive phenotype.