Intergeneration CAG expansion in a Wuhan juvenile-onset Huntington disease family

武汉一例青少年发病型亨廷顿病家族的代际CAG重复序列扩增

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Abstract

OBJECTIVE: To make early diagnosis of IT15 gene mutation in a Wuhan juvenile-onset Huntington disease (HD) family, for providing them with genetic counseling, and making preparation for the further research on pathogenesis and experimental therapy of HD. METHODS: According to the principle of informed consent, we extracted genomic DNA from peripheral blood samples and carried genetic diagnosis of pathogenic exon 1 of IT15 gene by modified touchdown PCR and DNA sequencing methods. RESULTS: Eight of twenty-five family members carried abnormal allele: III(10), III(12), III(14), IV(3), and V(2) carried (CAG) (48), IV(11) and IV(12) carried (CAG) (67), and IV(14) carried (CAG) (63), in contrast with the 8-25 CAG trinucleotides in the members of control group. IV(14) carried 15 more CAG trinucleotides than her father III(10). CONCLUSION: The results definitely confirm the diagnosis of HD and indicate the CAG trinucleotide repeat expansion of IT15 gene in this HD family. In addition, CAG expansion results in juvenile-onset and anticipation (characterized by earlier age of onset and increasing severity) of the patient IV(12).

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