FMR-1 CGG transitions in male and female carriers of fragile X

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134269

Nolin, S L; Lewis, III, F A; Ye, L L ^[1]

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1. New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States); and others

We have conducted a preliminary analysis of the CGG transitions observed among the offspring of fragile X male and female carriers using the PCR method of Brown et al. A strong familial clustering was observed in maternal inheritance of the fragile X chromosome. Fifty-eight premutation females passed their fragile X alleles to mutiple offspring (total 134). Forty-nine of these women had 106 children with the full mutation. Nine mothers (2 in the 60-69 repeat range, 6 in the 80-89 range, 1 in the 90-99 range) had a total of 19 premutation and 3 full mutation children. These data suggest that a premutation carrier with 1 premutation child has a reduced risk for full mutation offspring independent of her CGG repeat size. Familial clustering was also observed in transmitting males. The daughters of transmitting males showed surprisingly little variation in CGG repeat size among each set of daughters. In twelve sibling sets, the daughters were within 10 CGGs of each other, 6 sets were within 11-18 repeats, and one set was within 40 repeats. Taken together, the male and female carrier data support the concept of a sequence or structure within or close to the CGG repeat which influences the expansion of the repeat during its transmission from parent to child. We also found that in transmitting males with > 90 repeats, the repeat was often meiotically unstable. In 5 of these males, 44% (7/16) meioses showed a reduction 2-20 CGGs inherited and all 5 fathers had at least 1 daughter with a size reduction. This finding suggests that repeats > 90 may not be stably transmitted in spermatocytes.

• OSTI ID: 134269
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DNA SEQUENCING
GENES
GENETICS
HEREDITARY DISEASES
HUMAN X CHROMOSOME
INSTABILITY
MEIOSIS
MENTAL DISORDERS
MUTATIONS
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
SIZE