Aicardi-Goutieres syndrome display genetic heterogeneity with one locus (AGS1) on chromosome 3p21

We have studied 23 children from 13 families with a clinical diagnosis of A icardi-Goutieres syndrome. Affected individuals had developed an early-onse t progressive encephalopathy that was characterized by a normal head circum ference at birth, basal ganglia calcification, negative viral studies, and abnormalities of cerebrospinal fluid comprising either raised white cell co unts and/or raised levels of interferon-alpha. By means of genomewide linka ge analysis, a maximum-heterogeneity LOD score of 5.28 was reached at marke r D3S3563, with alpha =.48, where alpha is the proportion of families showi ng linkage. Our data suggest the existence of locus heterogeneity in Aicard i-Goutieres syndrome and highlight potential difficulties in the differenti ation of this condition from pseudo-TORCH (toxoplasmosis, rubella, cytomega lovirus, and herpes simplex virus types 1 and 2) syndrome.