A missense HTRA1 mutation expands CARASIL syndrome to the Caucasian population

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) (MIM 600142) is a heritable small vessel disease clinically characterized by nonhypertensive leukoencephalopathy associated with alopecia and spondylosis.1,–,3 First described by Maeda et al.2 in 1965, cases exclusively come from Japan and China.3,4 Beginning in young adulthood, patients develop progressive motor and cognitive impairment and usually die within 10 years.1 Centrifugally enlarged arteries with widespread loss of both medial smooth muscle cells and mural extracellular matrix are observed in the white matter and leptomeninges.5 In July 2009, Hara et al.6 described the HtrA serine protease 1 gene ( HTRA1 ) as the causative gene of CARASIL. Here we report for the first time a Caucasian patient with CARASIL harboring a novel HTRA1 mutation. ### Case reports. The proband (II-3) was a 34-year-old man who in 2006 presented to the Neurology Department because of unsteady gait, urinary urgency, and slurred speech. He had a history of 150-pack-year cigarette smoking and alcohol and cocaine abuse for 8 years. No hypertension, diabetes mellitus, or dyslipidemia was recorded. Before 18 years of age, he had developed severe alopecia with male-pattern baldness. On examination, cognitive function was preserved but …