Aicardi-Goutières syndrome displays genetic heterogeneity with one locus (AGS1) on chromosome 3p21

Abstract

We have studied 23 children from 13 families with a clinical diagnosis of Aicardi-Goutières syndrome. Affected individuals had developed an early-onset progressive encephalopathy that was characterized by a normal head circumference at birth, basal ganglia calcification, negative viral studies, and abnormalities of cerebrospinal fluid comprising either raised white cell counts and/or raised levels of interferon-alpha. By means of genomewide linkage analysis, a maximum-heterogeneity LOD score of 5.28 was reached at marker D3S3563, with alpha=.48, where alpha is the proportion of families showing linkage. Our data suggest the existence of locus heterogeneity in Aicardi-Goutières syndrome and highlight potential difficulties in the differentiation of this condition from pseudo-TORCH (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus types 1 and 2) syndrome.

Figure 1

Graph of multipoint HLOD scores against distance (in cM) from 3pter. Maximum HLOD = 5.28, with α=.48. Confidence limits are given as 1-LOD-unit and 3-LOD-unit support intervals

Figure 2

Pedigrees showing linkage (families 1–7) and pedigrees not showing linkage (families 8–13), as assigned by HOMOG analysis, with the most-likely haplotypes for region of interest on chromosome 3p. Unaffected children that were not genotyped have been excluded from the pedigrees displayed.

Figure 2

Pedigrees showing linkage (families 1–7) and pedigrees not showing linkage (families 8–13), as assigned by HOMOG analysis, with the most-likely haplotypes for region of interest on chromosome 3p. Unaffected children that were not genotyped have been excluded from the pedigrees displayed.