A novel RNASEH2B splice site mutation responsible for Aicardi–Goutieres syndrome in the Faroe Islands

• Published in: Acta Paediatrica
• Main Authors: Ostergaard, Elsebet, Joensen, Frodi, Sundberg, Karin, Duno, Morten, Hansen, Flemming J, Batbayli, Mustafa, Sørensen, Nicolina, Born, Alfred Peter
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2012
• Subjects: Faroe Islands
• Online Access: http://dx.doi.org/10.1111/j.1651-2227.2012.02807.x; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1651-2227.2012.02807.x; https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1651-2227.2012.02807.x

Abstract Aim: The aim of the study was to identify the genetic background for Aicardi–Goutieres syndrome (AGS) in the Faroe Islands. Methods: Four patients with AGS were identified. The patients had a variable phenotype, from a severe prenatal form with intrauterine foetal death to a milder phenotype, albeit still with an early onset, within the first 2–3 months. Results: A genome‐wide search for homozygosity revealed one single 15.6 Mb region of homozygosity on chromosome 13, which included RNASEH2B , where a splice site mutation c.322‐3C>G was identified. Screening of 170 anonymous Faroese controls revealed a carrier frequency of approximately 1.8%, corresponding to an incidence of AGS in the Faroe Islands of around 1 in 12 300. Conclusion: The previously identified RNASEH2B mutations comprise altogether 20 mutations (missense, nonsense and splice site) with all patients harbouring at least one missense mutation. The severe phenotype of the Faroese patients compared with the previously reported patients with RNASEH2B mutations may be caused by the presence of two null alleles (although some residual normal splicing cannot be ruled out), whereas patients with one or two missense mutations may have some, albeit abnormal, RNASEH2B proteins, and hence some residual activity of RNASEH2B, explaining their milder phenotype.