TITLE:
Phenotypic Variability in a Family with Aicardi-Goutières Syndrome Due to the Common A177T RNASEH2B Mutation
AUTHORS:
Victoria Tüngler, Franziska Schmidt, Steve Hieronimus, Claudio Reyes-Velasco, Min Ae Lee-Kirsch
KEYWORDS:
Aicardi-Goutières Syndrome; RNASEH2B; Interferon-α; Autoimmunity
JOURNAL NAME:
Case Reports in Clinical Medicine,
Vol.3 No.3,
March
13,
2014
ABSTRACT: Aicardi-Goutières syndrome (AGS) is a rare
inflammatory encephalopathy mimicking in
utero acquired viral infection. Cardinal findings comprise leukodystrophy, basal
ganglia calcifications and cerebral atrophy along with cerebrospinal fluid
lymphocytosis and elevated interferon-α. In the majority of cases AGS is
inherited as an autosomal recessive trait and caused by mutations in six genes
including RNASEH2A, RNASEH2B, RNASEH2C, TREX1, SAMHD1 and ADAR1, all of which encode enzymes acting on nucleic acid species.
Most patients present with first neurological signs in early infancy and
experience severe global developmental delay. Here, we report on the unusual
divergent phenotype of two
siblings who both carry the most frequent AGS causing p.A177T (c.529G > A) RNASEH2B mutation in the homozygous state. While one sibling showed a typical AGS
presentation with early onset and severe statomotor and mental impairment, the
older sibling was intellectually completely normal. She was only
diagnosed because of mild spasticity of the legs and serological signs of autoimmunity. These findings
highlight the phenotypic variability of AGS and suggest that AGS may be underdiagnosed among
children with mild cerebral palsy.