Scholarlink

Background <p>Recently, mutations affecting a microRNA-29 (miR-29)-binding site in the 3’-untranslated region of <i>COL4A1</i> 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.</p> Methods <p>A 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.</p> Results <p>The 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, <i>COL4A1</i> c.*32G &gt; T, was identified and found to be absent in both parents. Identity testing confirmed the biological parentage, classifying the c.*32G &gt; T variant as a de novo mutation.</p> Conclusions <p>The discovery of PADMAL in a patient with a de novo mutation indicates that <i>COL4A1</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年2月20日

查看全文
  • Fei Xie,
  • Shuang Li,
  • Xingyue Hu,
  • Wenyu Li

摘要

Background

Recently, 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.

Methods

A 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.

Results

The 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.

Conclusions

The 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.