Table 2.

GLRA1, GLRB, and SLC6A5-Related Hereditary Hyperekplexia: Modes of Inheritance and Methods of Variant Detection

GeneProportion of HPX Attributed to Mutation of GeneMOI 1Proportion of Probands with a Pathogenic Variant Identified by Method 2
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
GLRA1 61%-63%AD & AR~95%See footnote 5.
GLRB 12%-14%AD & AR11/121/12 6
SLC6A5 25%AR (rarely AD 7)24/24None reported

AD = autosomal dominant; AR = autosomal recessive; HPX = hereditary hyperekplexia; MOI = mode of inheritance

1.

~85% were AR and ~15% were AD [Thomas et al 2013].

2.

Since the study of Thomas et al [2013], additional affected individuals have been reported, many as case studies. For additional reported variants, see Human Genome Mutation Database [Stenson et al 2020].

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications

5.

Deletion of exons 1 through 7 is common in the Turkish population [Thomas et al 2015]. Deletion of exons 1 through 6 [Brune et al 1996] and of 4 through 7 have also been reported [Chung et al 2010].

6.
7.

From: Hereditary Hyperekplexia Overview

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.