Jara L, López M, Mellado C, Aspillaga M, Avendaño I, Blanco R
Departamento de Biología Celular y Genética, Facultad de Medicina, Universidad de Chile.
Rev Med Chil. 1998 Aug;126(8):911-8.
Fragile X syndrome is the most frequent cause of mental retardation linked to the X chromosome. In the majority of cases, the mutation responsible for the syndrome is an expansion of the trinucleotide repeat (CGG)n, present in the 5' region of exon 1 of the gene for mental retardation associated with fragile X syndrome (FMR-1).
To report the results of a fragile X screening in patients with mental retardation.
Fragile X screening using polymerase chain reaction methods was done in 386 X chromosomes from 300 patients (214 male), aged 4 to 26 years old. The modified Hagerman test was applied to male patients. Hybridization techniques were applied in a subgroup of 51 patients.
(CGG)n 30 was the allele found with the highest frequency in 50.2% of patients. (CGG)n 29 was found in 29% of patients. One subject had an allele with 46 CGG repeats, which corresponds to the gray zone. Hybridization studies were highly concordant with PCR, detecting four males with fragile X syndrome and a carrier female. The average clinical score of mental retardation not due to fragile X syndrome was 10.3 +/- 3.4 (range 3 to 23), and 97% of males had a score below 19. The concordance between scores over 20 and molecular genotype was 98%.
The distribution of (CGG)n repeats, observed in this study, was significantly different to that previously reported for a normal Chilean population. The dispersion of molecular status and clinical score was lower than previously described using cytogenetic techniques.
脆性X综合征是与X染色体相关的智力迟钝最常见的病因。在大多数病例中，导致该综合征的突变是三核苷酸重复序列（CGG）n的扩增，该序列存在于与脆性X综合征相关的智力迟钝基因（FMR - 1）外显子1的5'区域。
报告智力迟钝患者脆性X筛查的结果。
对300例年龄在4至26岁的患者（214例男性）的386条X染色体进行了使用聚合酶链反应方法的脆性X筛查。对男性患者应用改良的哈格曼试验。在51例患者的亚组中应用杂交技术。
（CGG）n 30是在50.2%的患者中发现的频率最高的等位基因。（CGG）n 29在29%的患者中被发现。一名受试者有一个含有46个CGG重复序列的等位基因，这对应于灰色区域。杂交研究与PCR高度一致，检测出4例脆性X综合征男性患者和1例携带者女性。非脆性X综合征所致智力迟钝的平均临床评分为10.3±3.4（范围3至23），97%的男性评分低于19。20分以上的评分与分子基因型之间的一致性为98%。
本研究中观察到的（CGG）n重复序列的分布与先前报道的智利正常人群的分布有显著差异。分子状态和临床评分的离散度低于先前使用细胞遗传学技术所描述的。
