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 Detectable 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 small intragenic deletions/insertions and missense, nonsense, and splice site variants; 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

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