Warter J M, Tranchant C
Service des Maladies du Système nerveux et du Muscle, Hôpitaux universitaires, Strasbourg.
Presse Med. 1998 Feb 28;27(8):376-81.
NEW TYPE OF MUTATION: Repeated sequences of nucleotide triplets can cause two groups of diseases.
These diseases result from an expansion of a noncoding portion of a gene which may be repeated more than 1000 times. This group includes several multisystem diseases such as the fragile X syndrome and its variants, Steinert's disease and Friedreich's disease in which nervous system disorders are not always predominant. The molecular mechanism of the cellular disorder is probably related to a nonfunctional abnormal protein.
Huntington's disease, spinobulbar amyotrophy or Kennedy's disease, dentato-rubo-pallidolusian atrophy and spinocerebellar ataxias 1, 2, 3, 6, and 7 are characterized by local expansion of the coding part of a gene. This low-amplitude expansion always involves the CAG triplet and leads to expression of a protein with an abnormal number of glutamines, producing typical neurodegenerative disease almost exclusively limited to the nervous system. The underlying mechanism of the neuronal suffering is probably the production of an abnormal but functional protein. The causes of this type of mutation remain unclear.
Positive diagnosis is now possible with DNA sequencing. While antenatal diagnosis offers essential information for family genetic counselling there is no perspective of therapeutic propositions for the near future. The problems raised by presymptomatic diagnosis must not be underestimated.
新型突变：核苷酸三联体的重复序列可引发两类疾病。
这些疾病源于基因非编码部分的扩增，该部分可能重复1000多次。这一类包括几种多系统疾病，如脆性X综合征及其变体、斯坦纳特病和弗里德赖希病，其中神经系统紊乱并非总是主要表现。细胞紊乱的分子机制可能与无功能的异常蛋白质有关。
亨廷顿病、脊髓延髓肌萎缩症或肯尼迪病、齿状核-红核-苍白球萎缩症以及脊髓小脑共济失调1型、2型、3型、6型和7型的特征是基因编码部分的局部扩增。这种低幅度扩增总是涉及CAG三联体，并导致表达一种谷氨酰胺数量异常的蛋白质，几乎专门产生仅限于神经系统的典型神经退行性疾病。神经元受损的潜在机制可能是产生一种异常但有功能的蛋白质。这种突变类型的原因尚不清楚。
现在通过DNA测序可以进行阳性诊断。虽然产前诊断为家庭遗传咨询提供了重要信息，但在不久的将来还没有治疗方案的前景。症状前诊断引发的问题不可低估。
