Neurologia · 2022
A variant in GRN of Spanish origin presenting with heterogeneous phenotypes.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Menéndez-González M, García-Martínez A, Fernández-Vega I, Pitiot A, Álvarez V
Аннотация
INTRODUCTION: The variant c.1414-1G>T in the GRN gene has previously been reported as probably pathogenic in subjects of Hispanic origin in the American continent.
METHODS: We report 5 families of Spanish origin carrying this variant, including the clinical, neuroimaging, and laboratory findings.
RESULTS: Phenotypes were strikingly different, including cases presenting with behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, rapidly progressive motor neuron disease (pathologically documented), and tremor-dominant parkinsonism. Retinal degeneration has been found in homozygous carriers only. Ex vivo splicing assays confirmed that the mutation c.1414-1G>T affects the splicing of the exon, causing a loss of 20 amino acids in exon 11.
CONCLUSIONS: We conclude that variant c.1414-1G>T of the GRN gene is pathogenic, can lead to a variety of clinical presentations and to gene dosage effect, and probably has a Spanish founder effect.
METHODS: We report 5 families of Spanish origin carrying this variant, including the clinical, neuroimaging, and laboratory findings.
RESULTS: Phenotypes were strikingly different, including cases presenting with behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, rapidly progressive motor neuron disease (pathologically documented), and tremor-dominant parkinsonism. Retinal degeneration has been found in homozygous carriers only. Ex vivo splicing assays confirmed that the mutation c.1414-1G>T affects the splicing of the exon, causing a loss of 20 amino acids in exon 11.
CONCLUSIONS: We conclude that variant c.1414-1G>T of the GRN gene is pathogenic, can lead to a variety of clinical presentations and to gene dosage effect, and probably has a Spanish founder effect.