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 Genetic Reevaluation of the Dutch Hyperekplexia Family

Marina A. J. Tijssen, MD; Rita Shiang, PhD; Judith van Deutekom, MSc; Rudolf H. Boerman, MD, PhD; John J. Wasmuth, PhD; Lodewijck A. Sandkuijl, MD; Rune R. Frants, PhD; George W. Padberg, MD, PhD
Arch Neurol. 1995;52(6):578-582. doi:10.1001/archneur.1995.00540300052012.
Text Size: A A A
Published online

Objectives:  To confirm linkage of the locus of the major form of hyperekplexia to markers on chromosome 5q, to screen for a point mutation in the gene encoding the α1 subunit of the glycine receptor, and to investigate whether the putative "minor" form of hyperekplexia, consisting of an excessive startle response without stiffness, is based on the same genetic defect as the major form.

Design:  A survey of various symptoms of hyperekplexia was performed in the Dutch pedigree. Linkage studies were performed for these symptoms.

Setting:  Subjects were visited at home, and the genetic study was performed at University Hospital Leiden, (the Netherlands).

Patients:  A history was taken from 76 subjects in the pedigree, and neurologic examinations were performed on 61 subjects from four generations of the pedigree. Main Outcome Measures: The main outcome measures were lod scores for markers on chromosome 5q for the major and minor forms of hyperekplexia and periodic leg movements during sleep. Mutations in the α1 subunit of the glycine receptor were detected by screening the exons with denaturing gradient gel electrophoresis.

Results:  Exaggerated startle responses were reported in 44 patients. The major form consisted of stiffness in addition to the excessive startle reaction and occurred in 28 subjects. Sixteen of 44 subjects had startle responses without stiffness, indicating the minor form. Linkage was found between markers CSF1-R, D5S209, and D5S119 and the disease locus for the major form, but not for the minor form. The α1 subunit of the glycine receptor showed a G to A transition mutation in codon 271 for the major form, but not for the minor form.

Conclusions:  Linkage and an abnormal glycine receptor were found only in the major form of hyperekplexia. Recognition of a major form is based on additional stiffness. This is therefore the most important diagnostic symptom. The minor form is not a different expression of the same genetic defect and may represent a normal but pronounced startle response.

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

Correspondence

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.
Submit a Comment

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();