OBJECTIVETo detect the mutations of Krit-1 gene that cause familial cerebral cavernous malformation (CCM) in the Han ethnic origin.

METHODSThe subjects were hospitalized in the Department of Neurosurgery, Tiantan Hospital affiliated to Capital University of Medical Sciences. Two families (A and B) and 8 apparently sporadic individuals affected with CCM were screened for mutations of Krit-1 gene. Members of the family CCM have a wide range in age of onset with seizures, headaches and skin lesions. The gene was screened by PCR amplification of 16 exons and mutation was detected by direct sequencing.

RESULTSIn family A samples, analysis of the Krit-1 gene revealed a new point mutation in exon 14 [a heterozygous C to G transition at nucleotide 1 289 (counting from the start codon or nt 2 308 counting from the first nt of the mRNA, aligned according to Gene Bank AF388384)] which predicts the substitution of a premature termination codon for Serine at codon 430 (S430X), belonging a nonsense point mutation. No mutation was identified in one of family A members as well as in any of the sporadic individuals with the exception of a single nucleotide polymorphism.

CONCLUSIONSReport the first family in the Han with CCM having a novel mutation in the CCM1 gene on the continent of Asia. The newly identified mutation creates a premature termination codon and is predicted to produce a truncated Krev1 interaction-trapped 1 protein, KRIT1. This result allows efficient presymptomatic molecular diagnosis.