Arrieta I, Gil A, Nuñez T, Telez M, Martinez B, Criado B, Lostao C
Departamento de Biología Animal y Genética, Facultad de Ciencias, Universidad del País Vasco, Bilbao, Spain.
Hum Biol. 1999 Feb;71(1):55-68.
The fragile X syndrome is an X-chromosome-linked dominant disorder with reduced penetrance. It is the most common inherited form of mental retardation. The molecular basis is usually the unstable expansion of a CGG trinucleotide repeat in the 5' untranslated region of the first exon of the FMR1 gene, which resides at chromosome position Xq27.3 and is coincident with the cytogenetic fragile site FRAXA, which characterizes the syndrome. In the Biscay province of the Basque Country the prevalence of FRAXA in a mentally retarded sample of non-Basque origin is in the range of other analyzed Spanish populations. In the sample of Basque origin we have not found FRAXA site expression and the repeat size is in the normal range. Based on this, we have examined FMR1 gene stability in normal individuals of Basque origin from the Biscay province. This study is based on a sample of 242 X chromosomes. The results from the CGG repeat region of FMR1 indicate that a prevalence of predisposing normal alleles toward repeat instability in the Basque population is 0.00% or near to it. This could be 1 of the explanations of the apparently low fragile X syndrome incidence found in the Basque mentally retarded sample analyzed by us. This low incidence does not seem to be associated with the flanking microsatellite markers.
脆性X综合征是一种X染色体连锁的显性疾病，其外显率降低。它是智力迟钝最常见的遗传形式。分子基础通常是FMR1基因第一个外显子5'非翻译区中CGG三核苷酸重复序列的不稳定扩增，该基因位于染色体Xq27.3位置，与细胞遗传学脆性位点FRAXA一致，后者是该综合征的特征。在巴斯克地区的比斯开省，非巴斯克血统的智力迟钝样本中FRAXA的患病率与其他分析过的西班牙人群范围相同。在巴斯克血统的样本中，我们未发现FRAXA位点表达，且重复序列大小在正常范围内。基于此，我们检测了比斯开省巴斯克血统正常个体中FMR1基因的稳定性。本研究基于242条X染色体的样本。FMR1基因CGG重复区域的结果表明，巴斯克人群中倾向于重复序列不稳定的正常等位基因患病率为0.00%或接近该值。这可能是我们分析的巴斯克智力迟钝样本中脆性X综合征发病率明显较低的原因之一。这种低发病率似乎与侧翼微卫星标记无关。
