CARASIL families from India with 3 novel null mutations in theHTRA1gene

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) (MIM 600142) is linked to homozygous mutations in the high-temperature requirement A serine peptidase 1 gene ( HTRA1 ).1 The triad includes alopecia, spondylosis deformans, and young-adult onset dementia following leukoaraiosis caused by cerebral small-vessel disease (CSVD).2 Although CARASIL originally was considered to be a recessive disorder and monoethnic, restricted to Japan, there are several reports of genetically confirmed cases and a few manifest heterozygotes in other ethnicities, thus expanding the CARASIL paradigm.3–6 In this study, we describe 3 CARASIL families carrying novel null HTRA1 mutations and also the notable phenotypes among the heterozygotes.