Mode of inheritance influences behavioral expression and molecular control of cognitive deficits in female carriers of the fragile X syndrome.
The effect of mode of inheritance on expression of fragile X syndrome [fra(X)] was investigated in nonretarded female carriers. Examination included cognitive and molecular measures. A priori predictions about cognitive impairment and size of an unstable region of DNA containing a CGG repeat on the X chromosome were tested in age and education matched heterozygotes grouped according to parental inheritance. Nine carriers with a maternal fra(X) chromosome, 11 carriers with a paternal fra(X) chromosome and 15 control mothers of children with non X-linked developmental disabilities were tested. Inheritance was established through DNA linkage analysis. Cognitive skills were assessed using the Wechsler Adult Intelligence Scale-Revised and the Benton Visual Retention Test. Molecular status was assessed by Southern blot analysis of genomic DNA digested with Eco RI and Eag I, and probed with StB 12.3. Results supported the inheritance models' predictions. Heterozygotes who inherited the fra(X) from their fathers appeared to be a homogeneous group. They were indistinguishable from controls on cognitive measures and all had genomic insertions of less than 500 base pairs. In contrast, heterozygotes who inherited the fra(X) chromosome from their mothers appeared to be made up of 2 sub-populations. They were as a group deficient in measures of attention and visual memory, but not other measures, with scores of some women consistently below the other subjects. Further, they had some members with greater than 500 base pair inserts.(ABSTRACT TRUNCATED AT 250 WORDS)
Hinton
V J
VJ
Queens College, C.U.N.Y., NY.
Dobkin
C S
CS
Halperin
J M
JM
Jenkins
E C
EC
Brown
W T
WT
Ding
X H
XH
Cohen
I L
IL
Rousseau
F
F
Miezejeski
C M
CM
D000328:Adult; D003072:Cognition Disorders / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005220:Fathers; D005260:Female; D005600:Fragile X Syndrome / Q000145:classification / Q000235:genetics* / Q000523:psychology*; D005784:Gene Amplification; D015870:Gene Expression; D006579:Heterozygote; D006801:Humans; D007360:Intelligence; D001523:Mental Disorders / Q000235:genetics*; D008875:Middle Aged; D008967:Molecular Biology; D009035:Mothers; D012091:Repetitive Sequences, Nucleic Acid
D004247:DNA