A pedigree study of pontine autosomal dominant microangiopathy and leukoencephalopathy caused by COL4A1 gene mutation in 3′-untranslated region
10.3760/cma.j.cn113694-20250217-00088
- VernacularTitle:COL4A1基因非翻译区变异导致的脑桥常染色体显性微血管病和脑白质病一家系研究
- Author:
Xiaoming QIN
1
;
Rong LI
;
Siyuan LIU
;
Chenhong LI
;
Shuai CHEN
;
Jiewen ZHANG
;
Fengyu WANG
Author Information
1. 河南省人民医院 阜外华中心血管病医院神经疾病科，郑州 451400
- Publication Type:Journal Article
- Keywords:
Cerebral small vessel diseases;
Pontine autosomal dominant microangiopathy and leukoencephalopathy;
COL4A1 gene;
3′-Untranslated region
- From:
Chinese Journal of Neurology
2025;58(10):1048-1056
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical and genetic characteristics of a Henan Han family with pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), aiming to enhance understanding of this disease.Methods:The proband was first admitted to the Department of Neurology, Henan Provincial People′s Hospital, Fuwai Central China Cardiovascular Hospital in December 2019 due to cerebral infarction and unilateral limb numbness and weakness. Detailed medical history collection, pedigree mapping, whole-exome sequencing screening, and Sanger sequencing validation were performed for the proband and family members. The patients′ clinical manifestations, imaging features, neuropsychological scale assessment results, and pathological changes were summarized, and genetic analysis was conducted on the gene variant site. Relevant literature was reviewed to summarize the characteristics of PADMAL.Results:The proband was a 47-year-old female, with 3 generations of family members affected, including 7 patients, 3 of whom had died. The clinical features of the patients were similar, with the first stroke occurring around the age of 40, without vascular risk factors such as hypertension or diabetes. The main clinical manifestation was unilateral limb numbness and weakness. The proband and her niece sought medical attention due to stroke symptoms. Brain magnetic resonance imaging revealed acute infarct lesions located in the pons, accompanied by multiple oval infarct foci (the "raisin bread sign") and white matter hyperintensity changes. Genetic testing showed that 4 patients carried a heterozygous c. *34GT mutation in the 3′-untranslated region (3′-UTR) of the COL4A1 gene, while the other 4 unaffected family members did not carry this variant, consistent with genotype- phenotype co-segregation in the family. Conclusions:PADMAL is an extremely rare monogenic cerebral small vessel disease caused by pathogenic variants in the 3′-UTR of the COL4A1 gene. The "raisin bread sign" in the pons is a relatively specific imaging feature that distinguishes it from other cerebral small vessel diseases. For patients with this sign, genetic testing for PADMAL should be considered.
