Moore S J, Strain L, Cole G F, Miedzybrodzka Z, Kelly K F, Dean J C
Department of Medical Genetics, Aberdeen Royal Hospitals Trust, Foresterhill, UK.
J Med Genet. 1999 Jul;36(7):565-6.
We report a 13 year old boy with fragile X syndrome resulting from a de novo deletion of the FMR1 and FMR2 genes extending from (and including) DXS7536 proximally to FMR2 distally. The patient has severe developmental delay, epilepsy, and behavioural difficulties, including autistic features. He has epicanthic folds, in addition to facial features typical of fragile X syndrome, and marked joint hypermobility. We compare our patient to the three other cases reported in which both FMR1 and FMR2 are deleted. This case has the smallest deletion reported to date. All four patients have epilepsy and a more severe degree of mental retardation than is usual in fragile X syndrome resulting from FMR1 triplet repeat expansion. Three of the patients have joint laxity and two have epicanthic folds. We suggest that these features, in particular severe developmental delay and epilepsy, may form part of the characteristic phenotype resulting from deletion of both FMR1 and FMR2 genes. The diagnosis in this case was delayed because routine cytogenetics showed no abnormality and standard molecular tests for FMR1 triplet repeat expansion (PCR and Southern blotting) failed. Further DNA studies should be undertaken to investigate for a deletion where clinical suspicion of fragile X syndrome is strong and routine laboratory tests fail.
我们报告了一名13岁男孩，患有脆性X综合征，病因是FMR1和FMR2基因的新发缺失，该缺失从近端的DXS7536（包括该位点）延伸至远端的FMR2。该患者有严重的发育迟缓、癫痫和行为困难，包括自闭症特征。除了具有脆性X综合征典型的面部特征外，他还有内眦赘皮，并且关节活动度明显增加。我们将我们的患者与其他三例报告的同时缺失FMR1和FMR2的病例进行了比较。该病例是迄今为止报告的最小缺失。所有四名患者都有癫痫，且智力发育迟缓程度比FMR1三联体重复扩增导致的脆性X综合征更为严重。其中三名患者有关节松弛，两名患者有内眦赘皮。我们认为这些特征，特别是严重的发育迟缓和癫痫，可能构成FMR1和FMR2基因均缺失所导致的特征性表型的一部分。该病例的诊断被延迟，因为常规细胞遗传学检查未发现异常，且针对FMR1三联体重复扩增的标准分子检测（PCR和Southern印迹法）均失败。当临床高度怀疑脆性X综合征而常规实验室检查失败时，应进行进一步的DNA研究以调查是否存在缺失。
