ClinVar

In a 29-year-old Romanian woman with autosomal recessive cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL; 600142), Bianchi et al. (2014) identified compound heterozygous mutations in the HTRA1 gene: a c.961G-A transition in exon 4, resulting in an ala321-to-thr (A321T) substitution at a highly conserved residue in the serine protease domain, and a 1-bp deletion (c.126delG; 602194.0007) in exon 1, resulting in a frameshift (Glu42fs) and premature termination at position 214. The missense mutation was inherited from the father and the truncating mutation from the mother. The mutations, which were found by direct sequencing of the HTRA1 gene, were not present in the dbSNP (build 137) or 1000 Genomes Project databases, or in 320 control chromosomes. The father showed mild supratentorial leukoencephalopathy and the mother showed diffuse infra- and supratentorial leukoencephalopathy, but both parents were neurologically normal, suggesting that the carrier condition may be paucisymptomatic. Functional studies of the variants were not performed.