0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
ARTICLE |

Molecular Predictors of Cognitive Involvement in Female Carriers of Fragile X Syndrome

Annette K. Taylor, MS, PhD; John F. Safanda; Majilinde Z. Fall, MA; Cindy Quince, MS; Kirsten A. Lang; Claire E. Hull; Isabelle Carpenter, BSN; Louise W. Staley, MS; Randi J. Hagerman, MD
JAMA. 1994;271(7):507-514. doi:10.1001/jama.1994.03510310037035.
Text Size: A A A
Published online

Objective.  —Fragile X syndrome is caused by a mutation involving expansion of a CGG trinucleotide repeat segment in the fragile X mental retardation—1 (FMR1) gene on the long arm of the X chromosome. This study was undertaken to determine the relative impact of three molecular characteristics of the FMR1 mutation— number of CGG repeats, methylation status, and X inactivation ratio—on the cognitive involvement of female carriers of fragile X syndrome.

Design.  —Retrospective study with new DNA analysis of known female carriers of fragile X syndrome.

Setting.  —Molecular studies were conducted in a university-based DNA diagnostic laboratory. Patients were originally ascertained through a regional fragile X clinic in a university-affiliated pediatric hospital.

Patients.  —Forty-eight female carriers of fragile X syndrome were studied, including 22 with a premutation (a small expansion to approximately 50 to 200 CGG repeats), 23 with a full mutation (a full expansion to >200 CGG repeats), and three with both types of mutations (mosaics).

Results.  —Median IQ score was significantly lower for females with a full mutation than for females with a premutation. No significant relationship was found between IQ score and number of CGG repeats or percentage methylation of the mutant allele within each mutation category. In addition, no significant relationship was found between IQ score and the proportion of normal FMR1 alleles on the active X chromosome in the carrier female group as a whole or in either mutation subgroup. Comparisons of leukocytes and saliva-borne epithelial cells in certain full-mutation carriers revealed striking differences in FMR1 mutation sizes.

Conclusions.  —Mutation category remains the most important predictor of affectedness in female carriers of fragile X syndrome. Our data do not support use of the proportion of normal FMR1 alleles on the active X chromosome as a predictor of cognitive involvement in female carriers with full mutations. Individual tissue-specific differences exist in the heterogeneous sizes of full mutations and in the presence of premutation/full-mutation mosaicism.(JAMA. 1994;271:507-514)

Topics

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Figures

Tables

References

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Sign in

Create a free personal account to sign up for alerts, share articles, and more.

Purchase Options

• Buy this article
• Subscribe to the journal

Related Content

Customize your page view by dragging & repositioning the boxes below.

Jobs
brightcove.createExperiences();