Table 1. [Molecular Genetic Testing Used in Usher Syndrome Type I (USH1)]. - GeneReviews® - NCBI Bookshelf

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Table 1.

Molecular Genetic Testing Used in Usher Syndrome Type I (USH1)

Gene ¹	USH1 Subtype	Proportion of USH1 Attributed to Pathogenic Variants ² in Gene ³	Proportion of Pathogenic Variants ² Detected by Method
Gene ¹	USH1 Subtype		Sequence analysis ⁴	Gene-targeted deletion/ duplication analysis ⁵
MYO7A	USH1B	53%-70%	~98% ⁶	<2% ⁷
USH1C	USH1C	6%-15% ⁸	>98%	2 reported ^9, 10
CDH23	USH1D	10%-20%	~85% ¹¹	<15% ¹²
PCDH15	USH1F	7%-12% ¹³	~75%	~25% ^14, 15
USH1G	USH1G	Rare (0%-4%)	>85%	2 reported ¹⁵
CIB2	USH1J	Unknown	1 reported ¹⁶	None reported ¹⁶
Unknown ¹⁷		10%-15% ¹⁸	NA

1.: See Table A. Genes and Databases for chromosome locus and protein.
2.: See Molecular Genetics for information on variants detected in this gene.
3.: Jouret et al [2019]
4.: 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.
5.: 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.
6.: Maubaret et al [2005], Jaijo et al [2007], Bonnet et al [2011], Roux et al [2011], Le Quesne Stabej et al [2012]
7.: The majority of reported pathogenic variants are detectable by sequence analysis; however, intragenic multiexon deletions have been reported [Adato et al 1997, Baux et al 2008, Roux et al 2011, Bonnet et al 2016].
8.: Almost all Usher syndrome type I in the Acadian population is caused by USH1C pathogenic variants. Five pathogenic variants in USH1C have been identified in 53 Acadian individuals with USH1 from Louisiana and Canada [Lentz et al, ongoing Natural History Study, unpublished]. Of these, c.216G>A is the most common variant (95/106 alleles, 90%), followed by c.238dupC (6/106 alleles, 6%).
9.: Sun et al [2018]
10.: Homozygous 11p15-p14 deletion syndrome (see Genetically Related Disorders) is caused by a contiguous gene deletion that includes USH1C and ABCC8 and has been observed in families from Saudi Arabia and Kuwait [Bitner-Glindzicz et al 2000, Al Mutair et al 2013].
11.: Bonnet et al [2011], Roux et al [2011], Le Quesne Stabej et al [2012]
12.: The majority of reported pathogenic variants are detectable by sequence analysis; however, intragenic deletions and duplications have been reported [Nakanishi et al 2010, Roux et al 2011, Aparisi et al 2014, Bonnet et al 2016].
13.: p.Arg245Ter (c.733C>T) is detected in a large percentage of Ashkenazi Jewish individuals with PCDH15-Usher syndrome type I.
14.: Roux et al [2011]
15.: Bonnet et al [2016]
16.: Riazuddin et al [2012]. Note: Booth et al [2018] suggest that CIB2 pathogenic variants cause DFNB48 and not USH1J.
17.: USH1E has been mapped to 21q21; USH1H has been mapped to 15q22-q23 [Ahmed et al 2009]; USH1K has been mapped to 10p11.21-q21.1 [Jaworek et al 2012].
18.: Bonnet et al [2011], Roux et al [2011], Le Quesne Stabej et al [2012], Yoshimura et al [2014], and personal communication with Kerry Goetz at eyeGENE.

From: Usher Syndrome Type I

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