Tissue-specific methylation differences and cognitive function in fragile X premutation females

Journal Article · Fri Aug 09 04:00:00 EDT 1996 · American Journal of Medical Genetics

DOI:https://doi.org/10.1002/(SICI)1096-8628(19960809)64:2<329::AID-AJMG19>3.3.CO;2-9· OSTI ID:478891

Allingham-Hawkins, D J; Babul, R; Chitayat, D ^[1]

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1. Hospital for Sick Children, Toronto (Canada); and others

Tissue-specific variation in (CGG){sub n} repeat size and methylation status of the FMR1 gene was investigated in 17 female premutation carriers. Minor variation in premutation repeat size among leukocyte, lymphoblast, and fibroblast tissues was noted in some subjects. One subject exhibited a premutation size allele of (CGG){sub 64} in leukocyte and fibroblast tissues by polymerase chain reaction analysis but a normal-size allele of (CGG){sub 46} in lymphoblast cells, suggesting low-level mosaicism in blood and clonality of the lymphoblast cell line. Six subjects exhibited differences in methylation pattern between leukocytes and lymphoblasts but not between leukocytes and fibroblasts, whereas 2 subjects showed large differences in methylation pattern between leukocytes and fibroblasts. Cognitive function was studied in 14 subjects using the Wechsler Adult Intelligence Scale-Revised. Mean Verbal and Performance IQs were well within the average range as was the mean Full Scale IQ; nevertheless, a trend toward lower Performance IQ compared with Verbal IQ was observed. No significant correlation was apparent between Full Scale IQ and (CGG){sub n} repeat size; however, a significant positive correlation was observed between Full Scale IQ and the proportion of the active X carrying the normal FMR1 allele in fibroblasts but not in leukocytes or lymphoblasts. 24 refs., 1 fig., 2 tabs.

• OSTI ID: 478891
• 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

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CORRELATIONS
DNA-CLONING
FEMALES
FIBROBLASTS
GENE MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN X CHROMOSOME
LEUKOCYTES
MENTAL DISORDERS
METHYLATION
MOSAICISM
NUCLEOTIDES
PHENOTYPE
POLYMERASE CHAIN REACTION
SIZE
TISSUE DISTRIBUTION