A second locus for Aicardi-Goutières syndrome at chromosome 13q14–21 (original) (raw)
A second locus for Aicardi-Goutières syndrome at chromosome 13q14–21
- M Ali1,
- L J Highet2,
- D Lacombe3,
- C Goizet3,
- M D King4,
- U Tacke5,
- M S van der Knaap6,
- L Lagae7,
- C Rittey8,
- H G Brunner9,
- H van Bokhoven9,
- B Hamel9,
- Y A Oade10,
- A Sanchis11,
- I Desguerre12,
- D Cau13,
- N Mathieu14,
- M L Moutard15,
- P Lebon16,
- D Kumar17,
- A P Jackson18,
- Y J Crow1,2
- 1Molecular Medicine Unit, University of Leeds, St James’s University Hospital, Leeds, UK
- 2Department of Clinical Genetics, St James’s University Hospital, Leeds, UK
- 3Medical Genetics Department, C.H.U. Bordeaux, Bordeaux, France
- 4Department of Paediatric Neurology, Children’s University Hospital, Dublin, Ireland
- 5Abteilung Neuropädiatrische, Universität Freiburg, Freiburg, Germany
- 6Department of Child Neurology, Free University Medical Center, Amsterdam, The Netherlands
- 7Department of Paediatric Neurology, Universitaire Ziekenhuizen, Leuven, Belgium
- 8Department of Paediatric Neurology, Sheffield Children’s Hospital, Sheffield, UK
- 9Department of Human Genetics, University Medical Centre, Nijmegen, The Netherlands
- 10Department of Paediatrics, Calderdale Royal Hospital, Halifax, UK
- 11Servicio de Pediatria, Hospital Universitario Dr Peset, Valencia, Spain
- 12Service de Neuropediatrie, Hôpital Necker, Paris, France
- 13Service de Pediatrie, Cherbourg, France
- 14Service de Genetique, Amiens, France
- 15Service de Neuropediatrie, Hôpital Cochin-Saint Vincent de Paul, Paris, France
- 16Service de Virologie, Hôpital Cochin-Saint Vincent de Paul, Paris, France
- 17Institute of Clinical Genetics, University Hospital of Wales, Cardiff, UK
- 18MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
- Correspondence to: Dr Yanick Crow Department of Clinical Genetics, Ashley Wing, St James’s University Hospital, Leeds, LS9 7TF, UK; yanick.crow{at}leedsth.nhs.uk
Abstract
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 α 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.
- AGS, Aicardi-Goutières syndrome
- HLOD, heterogeneity LOD
- IFN-α, interferon α
- LOD, logarithm of the odds
- AGS2
- Aicardi-Goutières syndrome
- interferon α
- intracranial calcification
- 13q14–21
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