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Biomedical subjects

W Oliver Tobin

Publications and source records attributed to W Oliver Tobin.

2 recordsLinked to original sources

Cognitive impairment as a manifestation of SPG7: case report.

Hereditary spastic paraplegia (HSP) is a group of genetic disorders caused by >80 genes that can be described as either pure or complex forms.We report a case of a patient with a complex form of SPG7 with significant cognitive impairment.A 42-year-old man presented with a 10-year history of dysarthria, 5 years of gait difficulties, and 3 years of cognitive symptoms. Neuropsychological analysis showed deficits involving speed of information processing, mental flexibility, ideational fluency, verbal concept formation, visual working memory, and visual-spatial perception. Next-generation sequencing on whole blood revealed 2 heterozygous pathogenic variants in SPG7 (c. 1049_1077del, p. Pro350Glnfs*36 and c. 1529C>T, p. Ala510Val).There are emerging reports of complex forms of SPG7 presenting with impairments in memory, executive dysfunction, language, visuospatial processing, social functioning, and emotional communication. In this report, we describe a complex SPG7 patient who underwent formal neuropsychological testing to assess cognitive status in depth. This revealed deficits in speed of processing, visuospatial working memory and perception, impaired non-verbal intellect, and overall lack of insight, which have not yet been described in the literature.

Cognitive impairment

Genomewide association study of a homogeneous multiple sclerosis cohort: Tumefactive demyelination.

BACKGROUND: Tumefactive demyelination (TD) is a rare variant of multiple sclerosis (MS) characterized by tumor-like lesions that often require aggressive management. Genome-wide association studies (GWAS) identified variants associated with MS; similar analyses in TD are lacking. OBJECTIVE: A GWAS was performed to identify variants associated with TD. METHODS: The case-control study included 142 TD cases and 293 controls. TD patients were required to have a demyelinating event and magnetic resonance imaging (MRI) showing one or more lesions. Controls were patients without a neurologic or systemic inflammatory disease or cancer. Logistic regression was used to compare cases versus controls for each variant; age, sex, and principal components were included as covariates. A p-value threshold of 5 × 10-8 was GWAS significant and 5 × 10-6 nominally significant. A polygenic risk score (PRS) was compared across TD and controls. RESULTS: Variants on chromosome 14 (rs117797734, p = 2.06 × 10-11, odds ratio (OR) = 13.14) and chromosome 6 (most significant rs6936540, p = 5.5 × 10-7, OR = 2.61) near DCBLD1 were significant. Seven non-MHC and two MHC variants associated with MS were associated with TD. The PRS was significantly higher in TD versus controls. CONCLUSION: We identified novel regions associated with TD, demonstrating the importance of performing GWAS in homogeneous subtypes of MS. Further validation and functional experiments are necessary.

Humans