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Normal transmitting males had a 150- to 400-base pair insertion that was inherited by their daughters either unchanged, or with small differences in size. Fragile X-positive individuals in the next generation had much larger fragments that differed among siblings and showed a generally heterogeneous pattern indicating somatic mutation. The mutated allele appeared unmethylated in normal transmitting males, methylated only on the inactive X chromosome in their daughters, and totally methylated in most fragile X males. However, some males had a mosaic pattern. Expression of the fragile X syndrome thus appears to result from a two-step mutation as well as a highly localized methylation. Carriers of the fragile X mutation can easily be detected regardless of sex or phenotypic expression, and rare apparent false negatives may result from genetic heterogeneity or misdiagnosis.<\/jats:p>","DOI":"10.1126\/science.252.5009.1097","type":"journal-article","created":{"date-parts":[[2006,10,5]],"date-time":"2006-10-05T18:10:16Z","timestamp":1160071816000},"page":"1097-1102","source":"Crossref","is-referenced-by-count":1174,"title":["Instability of a 550-Base Pair DNA Segment and Abnormal Methylation in Fragile X Syndrome"],"prefix":"10.1126","volume":"252","author":[{"given":"I.","family":"Oberl\u00e9","sequence":"first","affiliation":[{"name":"Laboratoire de G\u00e9netique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Rousseau","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9netique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Heitz","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9netique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Kretz","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9netique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Devys","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9netique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hanauer","sequence":"additional","affiliation":[{"name":"Laboratoire de G\u00e9netique Mol\u00e9culaire des Eucaryotes du CNRS, Unit\u00e9 184 de Biologie Mol\u00e9culaire et de G\u00e9nie G\u00e9n\u00e9tique de l'INSERM, Institut de Chimie Biologique, Facult\u00e9 de M\u00e9decine, 67085 Strasbourg C\u00e9dex, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bou\u00e9","sequence":"additional","affiliation":[{"name":"INSERM U73, Chateau de Longchamp, 75016 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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