Publication Date:
1991-05-24
Description:
The fragile X syndrome, a common cause of inherited mental retardation, is characterized by an unusual mode of inheritance. Phenotypic expression has been linked to abnormal cytosine methylation of a single CpG island, at or very near the fragile site. Probes adjacent to this island detected very localized DNA rearrangements that constituted the fragile X mutations, and whose target was a 550-base pair GC-rich fragment. 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oberle, I -- Rousseau, F -- Heitz, D -- Kretz, C -- Devys, D -- Hanauer, A -- Boue, J -- Bertheas, M F -- Mandel, J L -- New York, N.Y. -- Science. 1991 May 24;252(5009):1097-102.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratoire de Genetique Moleculaire des Eucaryotes du CNRS, Institut de Chimie Biologique, Faculte de Medecine, Strasbourg, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2031184" target="_blank"〉PubMed〈/a〉
Keywords:
Base Composition
;
DNA/*genetics
;
Female
;
Fragile X Syndrome/*genetics
;
Gene Rearrangement
;
Heterozygote Detection
;
Humans
;
Male
;
Methylation
;
*Mutation
;
Pedigree
;
Phenotype
;
Restriction Mapping
;
X Chromosome
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
