A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21.

1. J Med Genet. 2006 May;43(5):444-50. Epub 2005 May 20.

A second locus for Aicardi-Goutieres syndrome at chromosome 13q14-21.

Ali M(1), Highet LJ, Lacombe D, Goizet C, King MD, Tacke U, van der Knaap MS,
Lagae L, Rittey C, Brunner HG, van Bokhoven H, Hamel B, Oade YA, Sanchis A,
Desguerre I, Cau D, Mathieu N, Moutard ML, Lebon P, Kumar D, Jackson AP, Crow YJ.

Author information:
(1)Molecular Medicine Unit, University of Leeds, St James’s University Hospital,
Leeds, UK.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is an autosomal recessive, early
onset encephalopathy characterised by calcification of the basal ganglia, chronic
cerebrospinal fluid lymphocytosis, and negative serological investigations for
common prenatal infections. AGS may result from a perturbation of interferon
alpha metabolism. The disorder is genetically heterogeneous with approximately
50% of families mapping to the first known locus at 3p21 (AGS1).
METHODS: A genome-wide scan was performed in 10 families with a clinical
diagnosis of AGS in whom linkage to AGS1 had been excluded. Higher density
genotyping in regions of interest was also undertaken using the 10 mapping
pedigrees and seven additional AGS families.
RESULTS: Our results demonstrate significant linkage to a second AGS locus (AGS2)
at chromosome 13q14-21 with a maximum multipoint heterogeneity logarithm of the
odds (LOD) score of 5.75 at D13S768. The AGS2 locus lies within a 4.7 cM region
as defined by a 1 LOD-unit support interval.
CONCLUSIONS: We have identified a second AGS disease locus and at least one
further locus. As in a number of other conditions, genetic heterogeneity
represents a significant obstacle to gene identification in AGS. The localisation
of AGS2 represents an important step in this process.

DOI: 10.1136/jmg.2005.031880
PMCID: PMC2649012
PMID: 15908569 [Indexed for MEDLINE]

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