Knobloch O, Zoll B
Humangenetisches Institut, Universität Göttingen.
Monatsschr Kinderheilkd. 1992 Sep;140(9):646-51.
FORMULATION OF QUESTION: In 1991 four independent groups of geneticists succeeded in replacing the comparatively unreliable cytogenetic and indirect molecular diagnostics of the X-linked Martin-Bell-syndrome (MBS) by a more accurate approach.
Fine structure analysis of the disease locus at Xq 27.3 led to the discovery of the fragile X mental retardation gene I (FMR I-gene), the mutative changes of which are responsible for the disease and can easily be detected in Southern hybridizations with gene probes out of this area. The observed changes are strong amplification of a repetitive CGG-motive in exon I of the gene in patients, a more moderate one in symptom-free carriers of the disease and changes in the promotor region of the gene to a varying extent in patients and carriers.
This direct molecular diagnosis of MBS enables a safe identification of patients and carriers of the disease. A combined analysis of the observed mutations makes possible prenatal diagnosis, discriminating between carriers with and without symptoms. Especially this is necessary, since 20% of male and 50 to 70% of female mutation carriers are phenotypically normal.
问题的提出：1991年，四个独立的遗传学家小组成功地用一种更精确的方法取代了相对不可靠的细胞遗传学和间接分子诊断方法来诊断X连锁的马丁-贝尔综合征（MBS）。
对Xq 27.3处疾病位点的精细结构分析导致了脆性X智力低下基因I（FMR I基因）的发现，该基因的突变变化是导致该疾病的原因，并且可以很容易地在与该区域外的基因探针进行的Southern杂交中检测到。观察到的变化是患者基因外显子I中重复的CGG基序强烈扩增，疾病无症状携带者中扩增程度较轻，患者和携带者基因启动子区域有不同程度的变化。
这种对MBS的直接分子诊断能够安全地识别疾病患者和携带者。对观察到的突变进行综合分析使产前诊断成为可能，能够区分有症状和无症状的携带者。特别是这是必要的，因为20%的男性和50%至70%的女性突变携带者在表型上是正常的。
