Abnormal pattern detected in fragile-X patients by pulsed-field gel electrophoresis
- 1 February 1991
- journal article
- letter
- Published by Springer Nature in Nature
- Vol. 349 (6310), 624-626
- https://doi.org/10.1038/349624a0
Abstract
THE fragile-X syndrome is the most frequent inherited form of mental retardation, with an incidence of 1 in 1,500 males. It is characterized by the presence of a fragile site at Xq27.3 induced in vitro by folate deprivation or by inhibitors of deoxynucleotide synthesis1. Its mode of inheritance is unusual for an X-linked trait, with incomplete penetrance in both males and females. Some phenotypically normal males transmit the mutation to all their daughters who rarely express any symptoms, but penetrance is high in sons and daughters of these carrier women2. Genetic and physical mapping of the Xq27-q28 region has confirmed that the disease locus is located at or very near the fragile site3–6. Hypotheses proposed to account for the abnormalities in the inheritance of the disease include sequence rearrangements by meiotic recombination1,7,8 or a mutation that affects reactivation of an inactive X chromosome during differentiation of female germ cells9,10. To detect such rearrangements, or methylation changes that may reflect a locally inactive X chromosome, we used pulsed-field gel analysis of DNA from fragile-X patients with probes close to the fragile-X locus. The probe Do33 (DXS465) detected abnormal patterns in fragile-X patients, but not in normal controls or in non-expressing male transmitters.Keywords
This publication has 9 references indexed in Scilit:
- Isolation of the human chromosomal band Xq28 within somatic cell hybrids by fragile X site breakage.Proceedings of the National Academy of Sciences, 1990
- A New DNA Marker Tightly Linked to the Fragile X Locus ( FRAXA )Science, 1989
- CpG islands as gene markers in the vertebrate nucleusTrends in Genetics, 1987
- A model for the separation of large DNA molecules by crossed field gel electrophoresisNucleic Acids Research, 1987
- FRAGILE X SYNDROME: A UNIQUE MUTATION IN MANAnnual Review of Genetics, 1986
- Implications of fragile X expression in normal males for the nature of the mutationNature, 1986
- Genetic analysis of the fragile-X mental retardation syndrome with two flanking polymorphic DNA markers.Proceedings of the National Academy of Sciences, 1986
- A premutation that generates a defect at crossing over explains the inheritance of fragile X mental retardationAmerican Journal of Medical Genetics, 1985
- Further segregation analysis of the fragile X syndrome with special reference to transmitting malesHuman Genetics, 1985