A patient with pontine autosomal dominant microangiopathy and leukoencephalopathy caused by a de novo 3' untranslated region mutation of COL4A1 gene: case report and literature review.

backgroundRecently, mutations affecting a microRNA-29 (miR-29)-binding site in the 3'-untranslated region of COL4A1 have been identified as a cause of pontine autosomal dominant microangiopathy with leukoencephalopathy (PADMAL) and hereditary multi-infarct dementia (hMID) of the Swedish type. PADMAL and Swedish hMID are extremely rare disorders with no de novo mutations previously reported.

methodsA patient with cerebral small vessel disease underwent comprehensive neurological examinations, neuroimaging analysis, and whole-exome sequencing. Co-segregation analysis was performed on his family, and haplotype analysis was conducted to confirm the biological relationship.

resultsThe patient experienced recurrent ischemic strokes since age 32. Brain MRI showed multiple acute and chronic lacunar infarcts in the pons and bilateral cerebral hemispheres. A previously reported pathogenic mutation of PADMAL, COL4A1 c.*32G > T, was identified and found to be absent in both parents. Identity testing confirmed the biological parentage, classifying the c.*32G > T variant as a de novo mutation.

conclusionsThe discovery of PADMAL in a patient with a de novo mutation indicates that COL4A1 gene miR-29-binding site variant sequencing should be considered in patients exhibiting typical clinical and MRI features, even if there is no family history.