Cervical Spinal Involvement in a Chinese Pedigree With Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy Caused by a 3' Untranslated Region Mutation of COL4A1 Gene.
Background and Purpose- Pontine autosomal dominant microangiopathy and leukoencephalopathy, a recently defined subtype of cerebral small vessel disease, is associated with mutations in COL4A1 (collagen type IV alpha 1 chain) 3' untranslated region. We here describe a pontine autosomal dominant microangiopathy and leukoencephalopathy pedigree with COL4A1 mutation presenting both pontine and cervical spinal cord involvement. Methods- For the diagnostic purpose, brain and spinal magnetic resonance imaging scanning, skin biopsy, and whole-exome sequencing were performed on the patients in the pedigree. Suspected pathogenic variants were further confirmed by cosegregation analysis using Sanger sequencing in the family members. Results- We identified a mutation located at the binding site of miR-29 (microRNA-29) in 3' untranslated region of COL4A1(c.*32G>A). The pontine autosomal dominant microangiopathy and leukoencephalopathy patients in this pedigree carried this variant, whereas other healthy family members but one did not. Magnetic resonance imaging showed lesions in the pons, white matter, and cervical spinal cord. Skin biopsy revealed thickened basal lamina in vessels. Conclusions- For the first time, we reported cervical spinal involvement in pontine autosomal dominant microangiopathy and leukoencephalopathy and expanded the clinical spectrum of this disease.
['Zhao|Yu-Ying|YY|', 'Duan|Ruo-Nan|RN|', 'Ji|Lin|L|', 'Liu|Qi-Ji|QJ|', 'Yan|Chuan-Zhu|CZ|']
D020413:3' Untranslated Regions D044466:Asians D059345:Cerebral Small Vessel Diseases D002574:Cervical Vertebrae D024141:Collagen Type IV D017809:Fatal Outcome D005260:Female D006801:Humans D056784:Leukoencephalopathies D008297:Male D008875:Middle Aged D009154:Mutation D010375:Pedigree D011149:Pons
pedigree leukoencephalopathies mutation cerebral small vessel disease collagen brain magnetic resonance imaging