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, Journal Name: American Journal of Medical Genetics Journal Issue: 2 Vol. 64; ISSN 0148-7299; ISSN AJMGDA
- Country of Publication:
- United States
- Language:
- English
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BASIC STUDIES
BLOOD
CORRELATIONS
DETECTION
EPITHELIUM
GENE MUTATIONS
GENE REGULATION
GENES
GENETIC MAPPING
GENOTYPE
HEREDITARY DISEASES
HUMAN X CHROMOSOME
MENTAL DISORDERS
METHYLATION
MOSAICISM
MUTATION FREQUENCY
NUCLEOTIDES
ONTOGENESIS
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
TISSUE DISTRIBUTION