Читать книгу Protocols for High-Risk Pregnancies - Группа авторов - Страница 115

Most cases of fragile X syndrome are caused by an expansion in the number of CGG repeats in the FMR1 gene. The normal range of repeats is between 5 and 44. Repeat size of 45 to 54 is considered to be of intermediate expansion; 55 to 200 repeats is a premutation; and greater than 200 repeats represents a full mutation. With any number of repeats beyond 44, the region becomes unstable and can lead to expansion during gene replication in oogenesis but generally not spermatogenesis. Hence, a female carrier of CGG repeat number in the premutation range can transmit a full mutation to her offspring. A female carrier of an intermediate expansion, however, can transmit only a premutation but not a full mutation (therefore, risk is assumed by her grandchildren rather than children). A chromosome with a full mutation results in hypermethylation of the DNA, impaired transcription of the downstream FMRP protein, and impaired prenatal and postnatal brain development.