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Abstract #27990 Published in IGR 13-1
Genome-wide homozygosity mapping and next generation sequencing indentifies SAMHD1 mutations in a novel variant of Aicardi-Goutieres syndrome
Du Moulin M; Thiele H; Barczyk K; George C; Frosch M; Schwindt W; Roth J; Nurnberg P; Rutsch FEuropean Journal of Pediatrics 2010; 169: 380-381
Aicardi-Goutieres syndrome (AGS) is an inborn multisystemic disease, resembling intrauterine viral infection resulting in psychomotor retardation, spasticity and chilblain-like skin lesions. Diagnostic criteria include intracerebral calcifications and elevated interferon-(alpha) and pterins in cerebrospinal fluid. Patients present early in infancy and death usually occurs during childhood in a state of decerebration. In four adult siblings with unknown neuro-degenerative disease presenting with stenoses of intracranial vessels, stroke and glaucoma in childhood, genome wide homozygosity mapping identified 170 candidate genes embedded in a common haplotype of 8 Mb on chromosome 20q11-13. Next generation sequencing of the entire region identified the Arg164X mutation in SAMHD1, a gene most recently described in AGS, on both alleles in all affected siblings. In patient fibroblasts SAMHD1 protein was undetectable, while basal expression of interleukin-8 was increased and stimulated expression interferon-(beta) was reduced. We conclude that mutations in SAMHD1 by modulating intravascular cytokine expression lead to a novel phenotype of AGS.
M. Du Moulin. Munster University, Children's Hospital, Germany.
Classification:
9.4.15 Glaucoma in relation to systemic disease (Part of: 9 Clinical forms of glaucomas > 9.4 Glaucomas associated with other ocular and systemic disorders)
9.1.1 Congenital glaucoma, Buphthalmos (Part of: 9 Clinical forms of glaucomas > 9.1 Developmental glaucomas)