Table 1.

Molecular Genetic Testing Used in Nijmegen Breakage Syndrome

Gene 1MethodProportion of Pathogenic Variants 2 Detectable by Method
NBN Targeted analysis for c.657_661del5 variant 370%-100% 4
Sequence analysis 5~100%
Gene-targeted deletion/duplication analysis 6None reported 7
1.
2.

See Molecular Genetics for information on variants detected in this gene.

3.

Methods that may be used to detect the c.657_661del5 pathogenic variant can include allele-specific PCR, sequence analysis, and genotyping assays designed to detect this variant. Note that these assays may not detect variants other than the targeted variant.

4.

Nearly all affected individuals from Poland, the Czech Republic, and Ukraine tested to date are homozygous for the common pathogenic variant c.657_661del5. In a study of eight unrelated individuals with NBS from the Russian population, Resnick et al [2002] found that all but one of the 16 alleles were c.657_661del5. In the US, about 70% of individuals tested to date are homozygous for the common allele, 15% are heterozygous for c.657_661del5 and a second unique pathogenic variant, and 15% are homozygous for a unique pathogenic variant. Almost all affected individuals in the US who have the c.657_661del5 pathogenic variant are of known Eastern European ancestry.

5.

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.

6.

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.

7.

No large exon or multiexon deletions or duplications involving this gene have been reported to cause NBS.

From: Nijmegen Breakage Syndrome

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