Recurrent Hemorrhagic Stroke and Microcephaly in a Newborn with Aicardi-Goutières Syndrome Caused by a Homozygous Intronic RNASEH2B Variant.

Abstract

Aicardi-Goutières syndrome (AGS) is a progressive multisystem disorder marked by early-onset encephalopathy. This report investigates the genetic basis of AGS in a newborn from consanguineous parents with microcephaly, recurrent hemorrhagic strokes, brain calcifications, leukodystrophy, epilepsy, anemia, thrombocytopenia, and left ventricular hypertrophy. Next-generation sequencing-based targeted gene panel testing for epilepsy c.65-13G>A variant in the RNASEH2B gene. Both parents were identified as carriers of the heterozygous mutation, confirming autosomal recessive inheritance. RNA analysis showed that this variant created a new splice site, leading to an 11-base-pair extension in exon 2. This alteration caused a frameshift (p.Glu22Valfs*7) and subsequent truncation of the RNASEH2B protein. This case highlights the severe neurological manifestations of AGS in newborns and elucidates the pathogenic mechanism of a newly identified intronic RNASEH2B variant.