Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000192118 | SCV001451563 | pathogenic | Alexander disease | 2019-02-13 | criteria provided, single submitter | clinical testing | The GFAP c.259G>C (p.Val87Leu) missense variant is located in the helical rod domain of GFAP. The p.Val87Leu variant that has been reported in one study, in which it is found in a heterozygous state in a 31-year-old woman with Alexander disease (Suzuki et al. 2012). This patient was noted to have tonic-clonic seizures with treatment via anticonvulsants beginning as early as 10 months of age. She later presented with regression in mental function around age 15 and gait disturbance at age 25. Based on a neurological assessment in adulthood, her overall phenotype included psychomotor regression, seizures, pendular nystagmus, dysarthria, dysphagia, cerebellar ataxia, spastic gait, urine incontinence, and eventual palatal tremor. A brain MRI showed atrophy of the medulla oblongata and mild cervical cord atrophy, deep white matter abnormalities, periventricular rim, and signal changes of the medulla oblongata and dentate hilum. A head CT after a fall identified calcification in the subcortical and cortical regions (Suzuki et al. 2012). The p.Val87Leu variant is not found in the Genome Aggregation Database. The helical rod domain or central helical domain of GFAP is critical for interfilament network formation, filament assembly, and stabilization of subunits (Yoshida et al. 2007). Based on the application of ACMG criteria, the p.Val87Leu variant is classified as pathogenic for Alexander disease. |
| Epithelial Biology; Institute of Medical Biology, |
RCV000056876 | SCV000087989 | not provided | not provided | no assertion provided | not provided | ||
| Gene |
RCV000192118 | SCV000222977 | not provided | Alexander disease | no assertion provided | literature only |