Table 1.

Molecular Genetic Testing Used in PKAN and NBIA

Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
PANK2 Sequence analysis 3>99% of individuals with NBIA with "eye of the tiger" sign on MRI 4, 5
~50% of individuals with clinical diagnosis of NBIA
Gene-targeted deletion/duplication analysis 6~3%-5% 7
1.
2.

See Molecular Genetics for information on allelic 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.

NBIA International Mutation Database, Oregon Health & Science University, unpublished data

5.

Sequence analysis of the coding region and splice sites of PANK2 identifies at least one pathogenic variant in all individuals with the "eye of the tiger" sign on MRI. Preliminary data indicate that approximately 5% of individuals with clinical and radiographic evidence of PKAN demonstrate only one pathogenic variant by sequence analysis. Approximately 23% of families with PKAN have known or suspected consanguinity and 33% of families with PKAN demonstrate homozygous PANK2 pathogenic variants.

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.

Exon and multiexon deletions in PANK2 may not be detected by sequence analysis; several such alleles have been reported (see Table A).

From: Pantothenate Kinase-Associated Neurodegeneration

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