Thus, the CADASIL-like family disease may be caused by heterozygous HTRA1 gene mutation, which leads to autosomal dominant hereditary cerebral small vessel disease.
We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).
Therefore, HTRA1 represents another new gene to be considered in future studies of cerebral small-vessel diseases, as well as alopecia and degenerative vertebral/disk diseases.
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.
Mutations upregulating COL4A1 expression lead to PADMAL, a severe early onset ischemic cSVD, distinct from the various phenotypes associated with COL4A1 missense glycine mutations.Ann Neurol 2016;80:741-753.
Clinical features and diagnostic clues of these conditions, [cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), COL4A1-related cerebral small vessel diseases, autosomal dominant retinal vasculopathy with cerebral leukodystrophy (AD-RVLC), and Fabry's disease] are here reviewed.
In the present review article we will focus on the molecular basis of the COL4A1 stroke syndrome, summarize data on its variable phenotype, and explore additional questions concerning the possible genotype-phenotype correlations and the mechanisms leading to cerebral small-vessel disease in this clinically heterogeneous condition.
Larger population studies are needed to confirm these findings and to test the hypothesis that the GLA g.1170C>T may contribute to the multifactorial risk of ischaemic small-vessel cerebrovascular disease.