title: Familial Aicardi-Goutières syndrome due to SAMHD1 mutations is associated with chronic arthropathy and contractures.
abstract: We report on two siblings doubly heterozygous for null mutations in the recently identified AGS5 gene SAMHD1. The older female child showed mild intellectual disability with microcephaly. Her brother demonstrated a significant spastic paraparesis with normal intellect and head size. Both children had an unclassified chronic inflammatory skin condition with chilblains, and recurrent mouth ulcers. One child had a chronic progressive deforming arthropathy of the small and large joints, with secondary contractures. This family illustrate the remarkable phenotypic diversity accruing from mutations in genes associated with Aicardi-Goutières syndrome (AGS). The association of arthropathy with SAMHD1 mutations highlights a phenotypic overlap of AGS with familial autoinflammatory disorders such as chronic infantile neurological cutaneous and articular syndrome (CINCA). This family therefore illustrate the need to consider mutation analysis of SAMHD1 in non-specific inflammatory phenotypes of childhood. We propose that arthropathy with progressive contractures should now be considered part of the spectrum of Aicardi-Goutières syndrome because of SAMHD1 mutations.
authors.affiliation: Institute of Neuroscience and Muscle Research, University of Sydney, Sydney, Australia. russelld@chw.edu.au
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.forename: Hannah
authors.initials: H
authors.lastname: Gornall
authors.forename: Davinder
authors.initials: D
authors.lastname: Singh-Grewal
authors.forename: Melanie
authors.initials: M
authors.lastname: Alcausin
authors.forename: Gillian I
authors.initials: GI
authors.lastname: Rice
authors.forename: Yanick J
authors.initials: YJ
authors.lastname: Crow
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003286:Contracture / Q000150:complications / Q000235:genetics*; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007592:Joint Diseases / Q000150:complications / Q000235:genetics*; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D011247:Pregnancy; D000076106:SAM Domain and HD Domain-Containing Protein 1; D013577:Syndrome; D014581:Urticaria / Q000150:complications / Q000235:genetics
chemical_list: D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins