A 33-year diagnostic odyssey in an Ashkenazi Jewish patient with Aicardi-Goutières syndrome

Abstract

The critical need for awareness and genetic testing of the SAMHD1 deletion in Ashkenazi Jewish patients is highlighted owing to its relatively high carrier frequency. Early detection can prevent severe disease complications through targeted therapy.

Keywords: Aicardi-Goutières syndrome; SAMHD1; carrier screening; copy number variation; genetic testing; interferonopathies.

Fig 1

Family pedigree and patient presentation. A, Pedigree chart illustrating inheritance pattern of SAMHD1 deletion. Carriers marked with central circle (carrier status of II.3 is unknown). Patient indicated with black arrow. B, Chilblain-like skin lesions observed on the patient’s feet and hands. C, Computed tomography scan showing ependymal calcifications in the lateral ventricles. D, Integrated Genome Viewer visualization of SAMHD1 exons 1 to 3 in the patient (II.1), father (I.1), mother (I.2), and healthy control (HC).

Fig 2

Genetic analysis and expression profiling of SAMHD1. A, PCR amplification of SAMHD1 fragment from genomic DNA of family members and healthy control (HC). An approximately 500-bp PCR product is generated in the patient and carrier parents but not in the patient’s brother or HC. B, Sanger sequencing of PCR fragment shows breakpoints of deletion. C, Normalized expression of SAMHD1 and ISG15 in the family and HC. D, NanoString analysis of interferon-stimulated genes in the patient and HCs.