This case provides a detailed clinical and imaging description of CADASIL associated with NOTCH3 c.3313G > T (p.Gly1105Cys) and expands understanding of genotype–phenotype correlations among exon 20 variants and found marked phenotypic heterogeneity across variants and populations.
This case adds longitudinal clinical, neuroimaging, ophthalmological, and neuropsychological data to the limited literature on patients carrying the p.Arg272His variant, supporting further investigation of genotype–phenotype relationships in ARSACS.
Vincenzo Sortino, A. Sapuppo, Anastasia Bernabini et al.· Neurogenetics· 0 citations
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, inherited cerebral microvascular disease primarily caused by mutations in the NOTCH3 gene, leading to a spectrum of neurological symptoms including recurrent strokes, cognitive decline, migraine with aura, and mood disturbances. This report presents the clinical course of a 52-year-old male patient who presented with neurological symptoms beginning at age 50 and was subsequently diagnosed with CADASIL following genetic analysis. Notably, the patient also exhibited early-onset epilepsy, a less common finding in CADASIL which typically manifests later. A further unique aspect was concurrent thrombophilia, complicating treatment significantly. Initial anticoagulant therapy resulted in a new ischemic event, necessitating a switch to dual antiplatelet therapy due to CADASIL's microbleed risk. This case underscores CADASIL's diagnostic complexities, especially with comorbid genetic factors and atypical presentations like early epilepsy, stressing the need for multidisciplinary care and individualized risk-benefit assessments in management.
Sinem Fidan Buçin, Hatice Karaer Ünaldi, Fatma Nur Birgin et al.· Sanatorium Medical Journal· 0 citations
The broad clinical spectrum associated with the SEPTIN9 R106W mutation in a Chinese pedigree spanning from childhood to adulthood is delineated, highlighting the critical role of active inter vention in childhood-onset HNA.
Jing Chen, Shuang Chen, Xin-Yi Zhu et al.· Frontiers in Genetics· 0 citations
Arterial Tortuosity Syndrome (ATS) is a rare autosomal recessive connective tissue disorder caused by pathogenic variants in SLC2A10, which encodes the facilitative glucose transporter GLUT10. Although its vascular features are well recognized, the molecular consequences of many truncating variants remain poorly understood. We report a patient with ATS carrying a homozygous nonsense variant, c.485G > A (p.Trp162Ter), identified by whole-exome sequencing. Quantitative real-time PCR assessed SLC2A10 expression, and integrated bioinformatic analyses (structural modeling, druggability prediction, transmembrane topology, molecular docking, and molecular dynamics) explored its structural impact. The patient presented with severe systemic arterial tortuosity, congenital cardiovascular anomalies, hernias, connective tissue abnormalities, and neurovascular involvement involving cerebral tortuosity and distal intracranial narrowing. Structural modeling revealed extensive truncation of GLUT10 and loss of multiple α-helical domains, with transmembrane helices reduced from twelve to five. Docking of nine known ligands showed weaker binding to the mutant, and Compound 892 bound most strongly to the wild type (−7.469 kcal/mol). Across 300 ns simulations, the mutant complex proved markedly less stable. qRT-PCR showed no significant transcript differences among patient, carriers, and controls. Our findings broaden the neurovascular spectrum of SLC2A10-related ATS and demonstrate that p.(Trp162Ter) severely disrupts GLUT10 architecture, topology, and ligand binding.
Serdar Bozlak, Cüneyd Yavaş, Evrim Yalcin et al.· International Journal of Mol...· 0 citations
The first genetically confirmed Iranian patient, an 18‐month‐old boy presenting with profound developmental delay, axial hypotonia, limb hypertonia, dystonia, oculogyric crises, ptosis, and autonomic dysfunction is reported, expanding the mutational spectrum of SLC18A2‐related disease and highlighting the importance of early genetic diagnosis.
Ali Nikkhah, R. Badv, S. Habibi et al.· Case Reports in Neurological...· 0 citations
The novel NR2F1 variant was classified as likely pathogenic according to ACMG guidelines, confirming the diagnosis of BBSOAS and the ARF3 variant, identified as a secondary finding of uncertain clinical significance, is unlikely to account for the patient's phenotype.
Sina Babaei, Haneieh Honarmand, Mortaza Bonyadi et al.· Molecular Biology Reports· 0 citations
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