Seki N, Ishikiriyama S, Yamauchi M, Hori T
Division of Genetics, National Institute of Radiological Science, Chiba.
Jpn J Genet. 1994 Jun;69(3):259-67. doi: 10.1266/jjg.69.259.
Fragile X syndrome is the most common familial form of mental retardation and known to be associated with the fragile site at Xq27.3 (FRAXA). The syndrome has recently been characterized by a unique genetic mechanism which involves dynamic mutation due to a heritable unstable DNA sequence, p(CCG)n repeat, in the FRAXA locus. We were asked to make a genetic diagnosis on the case of a normal male who has two brothers and a maternal uncle with mental retardation. We performed the pedigree analysis of the fragile X syndrome using both cytogenetic and molecular techniques. The affected two brothers and the uncle showed cytogenetic expression of the fra (X)(q27.3) and carried hypermethylated full mutation in the FRAXA locus. The phenotypically normal mother also exhibited fragile X expression and was found to be a carrier of premutation. Via female transmission, the premutation converted to full mutation and exhibited somatic heterogeneity and hypermethylation. However, both cytogenetic and molecular data did not show any evidence of fragile X mutation in the normal male client and, thus, excluded the possibility of his being a carrier.
脆性X综合征是最常见的家族性智力障碍形式，已知与Xq27.3（FRAXA）处的脆性位点有关。最近，该综合征的特征是一种独特的遗传机制，涉及由于FRAXA基因座中可遗传的不稳定DNA序列p(CCG)n重复导致的动态突变。我们被要求对一名正常男性进行基因诊断，该男性有两个患有智力障碍的兄弟和一个舅舅。我们使用细胞遗传学和分子技术对脆性X综合征进行了系谱分析。受影响的两个兄弟和舅舅表现出fra(X)(q27.3)的细胞遗传学表达，并在FRAXA基因座携带高甲基化的完全突变。表型正常的母亲也表现出脆性X表达，并且被发现是前突变的携带者。通过女性传递，前突变转化为完全突变，并表现出体细胞异质性和高甲基化。然而，细胞遗传学和分子数据均未显示正常男性客户存在脆性X突变的任何证据，因此排除了他为携带者的可能性。
