Table 1. [Molecular Genetic Testing Used in IRF6-Related Disorders]. - GeneReviews® - NCBI Bookshelf

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Table 1.

Molecular Genetic Testing Used in IRF6-Related Disorders

Gene ¹	Phenotype	Proportion of Probands with a Pathogenic Variant ² Detectable by Method
Gene ¹	Phenotype	Sequence analysis ³	Deletion/duplication analysis ⁴
IRF6	VWS	~72% ⁵	<2% ⁶
	PPS	~97% ⁷	Unknown ⁸
	Isolated NTD	2 persons ⁹	None reported
	Isolated OFC	18 persons ¹⁰	None reported

: NTD = neural tube defect; OFC = orofacial cleft; PPS = popliteal pterygium syndrome; VWS = Van der Woude syndrome
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.: 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 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.: Sequence analysis of IRF6 (exons 1-9) detects pathogenic variants in approximately 68% of individuals with VWS [de Lima et al 2009]. Pathogenic variants in exons 3, 4, 7, and 9 account for 80% of known VWS-causing variants (N=307) [de Lima et al 2009].
6.: Whole- and partial-gene deletions have been identified in several families with VWS [Sander et al 1994, Schutte et al 1999, Kayano et al 2003, Osoegawa et al 2008, Tan et al 2008, de Lima et al 2009, Salahshourifar et al 2011, Mbuyi-Musanzayi et al 2020].
7.: Sequence analysis of exon 4 of the IRF6 coding region detected pathogenic variants in approximately 72% of individuals with PPS [de Lima et al 2009]. Additional sequencing of the entire coding region of IRF6 detected pathogenic variants in approximately 97% of individuals with PPS (N=37) [de Lima et al 2009].
8.: Incidence of deletions/duplications unknown; likely rare as pathogenic variants were identified on sequence analysis in 36 of 37 individuals with PPS [de Lima et al 2009].
9.: Kousa et al [2019]
10.: IRF6 pathogenic variants were identified in 0.47% (18/3,811) of individuals with nonsyndromic orofacial cleft [Leslie et al 2016, Khandelwal et al 2017].

From: IRF6-Related Disorders

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