Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
Cerebral small vessel disease associated with COL4A1 and COL4A2 duplication: clinical and MRI features resembling CADASIL.
СтатьяКлинический случайНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Chen Lili, Li Shuang, Xie Fei, Hu Xingyue, Lv Wen
Аннотация
BACKGROUND: Large duplications or triplications involving the 13q33-34 chromosomal region, which encompass the COL4A1 and COL4A2 genes, have been reported in association with cerebral small vessel disease (CSVD) in a few patients. Herein, we report an additional case of CSVD linked to a duplication of COL4A1 and COL4A2 and provide a detailed summary of the associated clinical and MRI findings.
METHODS: A patient with CSVD underwent detailed clinical and neuroimaging evaluations. Targeted next-generation sequencing (NGS) and copy number variation sequencing (CNV-seq) based on whole genome sequencing were used to identify the genetic basis of the disease.
RESULTS: The patient experienced his first ischemic stroke at age 51. Cranial MRI revealed extensive acute and chronic lacunar infarcts and white matter hyperintensities across both cerebral hemispheres, with involvement of the anterior temporal lobe and the external capsule. Bilateral thalamic microbleeds were also noted. The clinical features and MRI findings are similar to those observed in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Targeted NGS and CNV-seq analysis identified a duplication in the region of chromosome 13, which included the COL4A1 and COL4A2 genes.
CONCLUSIONS: This case provides further evidence supporting the association of CNVs in COL4A1 and COL4A2 with CSVD. When hereditary CSVD is suspected and no micro-mutations in CSVD-associated genes are identified, CNV analysis of the 13q region should be considered.
METHODS: A patient with CSVD underwent detailed clinical and neuroimaging evaluations. Targeted next-generation sequencing (NGS) and copy number variation sequencing (CNV-seq) based on whole genome sequencing were used to identify the genetic basis of the disease.
RESULTS: The patient experienced his first ischemic stroke at age 51. Cranial MRI revealed extensive acute and chronic lacunar infarcts and white matter hyperintensities across both cerebral hemispheres, with involvement of the anterior temporal lobe and the external capsule. Bilateral thalamic microbleeds were also noted. The clinical features and MRI findings are similar to those observed in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Targeted NGS and CNV-seq analysis identified a duplication in the region of chromosome 13, which included the COL4A1 and COL4A2 genes.
CONCLUSIONS: This case provides further evidence supporting the association of CNVs in COL4A1 and COL4A2 with CSVD. When hereditary CSVD is suspected and no micro-mutations in CSVD-associated genes are identified, CNV analysis of the 13q region should be considered.