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

doi: 10.1086/302955. Epub 2000 May 25.

A P Jackson, E Roberts, E van Beusekom, P Barth, P Corry, C D Ferrie, B C Hamel, R Jayatunga, G Karbani, R Kálmánchey, A Kelemen, M King, R Kumar, J Livingstone, R Massey, R McWilliam, A Meager, C Rittey, J B Stephenson, J L Tolmie, A Verrips, T Voit, H van Bokhoven, H G Brunner, C G Woods

Affiliations

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

Y J Crow et al. Am J Hum Genet. 2000 Jul.

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.

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Figures

Figure 1

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

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

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.

References

Electronic-Database Information

    1. Center for Medical Genetics, Marshfield Medical Research Foundation, http://www.marshmed.org/genetics/ (for information regarding marker order and relative genetic distances)
    1. Genome Database, http://gdbwww.gdb.org/ (for information on polymorphic markers on chromosome 3p)
    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for Aicardi-Goutières syndrome [MIM 225750] and pseudo-TORCH syndrome [MIM 251290])

References

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