A fragile X mosaic male with a cryptic full mutation detected in epithelium but not in blood
- Genetics and IVF Institute, Fairfax, VA (United States); and others
Individuals with developmental delay who are found to have only fragile X premutations present an interpretive dilemma. The presence of the premutation could be an unrelated coincidence, or it could be a sign of mosaicism involving a full mutation in other tissues. To investigate three cases of this type, buccal epithelium was collected on cytology brushes for Southern blot analysis. In one notable case, the blood specimen of a boy with developmental delay was found to have a premutation of 0.1 extra kb, which was shown by PCR to be an allele of 60 {+-} 3 repeats. There was no trace of a full mutation. Mosaicism was investigated as an explanation for his developmental delay, although the condition was confounded by prematurity and other factors. The cheek epithelium DNA was found to contain the premutation, plus a methylated full mutation with expansions of 0.9 and 1.5 extra kb. The three populations were nearly equal in frequency but the 1.5 kb expansion was the most prominent. Regardless of whether this patient has clinical signs of fragile X syndrome, he illustrates that there can be gross tissue-specific differences in molecular subpopulations in mosaic individuals. Because brain and epithelium are more closely related embryonically than are brain and blood, cryptic full mutations in affected individuals may be evident in epithelial cells while being absent or difficult to detect in blood. This phenomenon may explain some typical cases of the fragile X phenotype associated with premutations or near-normal DNA findings. 21 refs., 1 fig., 1 tab.
- OSTI ID:
- 478887
- Journal Information:
- American Journal of Medical Genetics, Vol. 64, Issue 2; Other Information: PBD: 9 Aug 1996
- Country of Publication:
- United States
- Language:
- English
Similar Records
Mild clinical involvement in two males with a large FMR1 premutation
Extreme variation between blood and fibroblast DNA patterns in mosaic fragile X males
Related Subjects
BASIC STUDIES
PATIENTS
HEREDITARY DISEASES
MENTAL DISORDERS
PHENOTYPE
GENES
GENE MUTATIONS
GENETIC MAPPING
MUTATION FREQUENCY
GENE REGULATION
TISSUE DISTRIBUTION
DETECTION
HUMAN X CHROMOSOME
MOSAICISM
BLOOD
ONTOGENESIS
EPITHELIUM
NUCLEOTIDES
METHYLATION
GENOTYPE
CORRELATIONS
POLYMERASE CHAIN REACTION