Phương pháp này cũng có thể được sửa đổi để xác định tình trạng methyl hóa của gen (ảnh hưởng chính trên biểu hiện gen bình thường FMR-1). Trong chẩn đoán trước khi sinh, methyl hóa phân tích là có vấn đề do sự hiện diện của mô hình methyl hóa của thai nhi | ABC of Clinical Genetics FRAX-A analysis. This method can also be modified to determine the methylation status of the gene the main influence on normal FMR-1 gene expression . In prenatal diagnosis methylation analysis is problematic owing to the presence of fetal methylation patterns and the size of the repeat becomes the most reliable predictive indicator. Huntington disease HD HD is a progressive fatal neurodegenerative disease. Like FRAX-A HD is caused by a triplet repeat expansion. The HD expansion involves a CAG triplet in exon 1 of the IT15 gene on chromosome 4. The expansion is translated into a polyglutamine tract in the huntingtin protein gene product that is believed to cause a dominant gain of function leading to neuronal loss. In normal individuals the CAG unit in exon 1 has between 9 and 35 repeats. Affected individuals have repeats of 36 units or greater with over 90 of affected subjects having 40-55 repeats. In general the greater the number of repeats an individual has the earlier the age of onset will be although this relationship is stronger for higher repeat numbers. Since the CAG repeat expansion is the sole mutation responsible for all HD cases molecular genetic analysis concentrates on this single region. Small CAG expansions can be detected using PCR amplification of the repeat region. The PCR products are then sized using polyacrylamide gel electrophoresis. Samples with known repeat sizes may be used as controls to determine the size of the expansion. Larger expansions cannot be detected by PCR and the time-consuming Southern blotting method must be used in cases where two normal sized repeat alleles are not detected by PCR. Charcot-Marie-Tooth disease CMT CMT disease or hereditary motor and sensory neuropathy HMSN is clinically and genetically heterogeneous but is generally characterised by wasting and weakness of the distal limb muscles with or without distal sensory loss. CMT may be inherited in an autosomal dominant autosomal recessive
