SAMHD1 compound heterozygous rare variants associated with moyamoya and mitral valve disease in the absence of other features of Aicardi-Goutières syndrome.

Autor: Karla AR; Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Pinard A; Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Boerio ML; Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Hemelsoet D; Department of Neurology, Ghent University Hospital, Ghent, Belgium., Tavernier SJ; Department of Internal Medicine and Pediatrics, Center for Primary Immunodeficiency, Jeffrey Modell Diagnosis and Research Center, Ghent University Hospital, Ghent, Belgium., De Pauw M; Department of Cardiology, Ghent University Hospital, Ghent, Belgium., Vereecke E; Department of Radiology, Ghent University Hospital, Ghent, Belgium., Fraser S; Division of Child Neurology, Department of Pediatrics, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Bamshad MJ; Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington, USA., Guo D; Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA., Callewaert B; Center for Medical Genetics Ghent, Ghent University Hospital, Ghent, Belgium.; Department of Biomolecular Medicine, Ghent University, Ghent, Belgium., Milewicz DM; Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Apr; Vol. 194 (4), pp. e63486. Date of Electronic Publication: 2023 Dec 01.
DOI: 10.1002/ajmg.a.63486
Abstrakt: Aicardi-Goutières syndrome (AGS) is an autosomal recessive inflammatory syndrome that manifests as an early-onset encephalopathy with both neurologic and extraneurologic clinical findings. AGS has been associated with pathogenic variants in nine genes: TREX1, RNASEH2B, RNASEH2C, RNASEH2A, SAMHD1, ADAR, IFIH1, LSM11, and RNU7-1. Diagnosis is established by clinical findings (encephalopathy and acquired microcephaly, intellectual and physical impairments, dystonia, hepatosplenomegaly, sterile pyrexia, and/or chilblains), characteristic abnormalities on cranial CT (calcification of the basal ganglia and white matter) and MRI (leukodystrophic changes), or the identification of pathogenic/likely pathogenic variants in the known genes. One of the genes associated with AGS, SAMHD1, has also been associated with a spectrum of cerebrovascular diseases, including moyamoya disease (MMD). In this report, we describe a 31-year-old male referred to genetics for MMD since childhood who lacked the hallmark features of AGS patients but was found to have compound heterozygous SAMHD1 variants. He later developed mitral valve insufficiency due to recurrent chordal rupture and ultimately underwent a heart transplant at 37 years of age. Thus, these data suggest that SAMHD1 pathogenic variants can cause MMD without typical AGS symptoms and support that SAMHD1 should be assessed in MMD patients even in the absence of AGS features.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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