Table 1.

Molecular Genetic Testing Used in Hereditary Paraganglioma-Pheochromocytoma Syndromes

Gene 1, 2Proportion of Hereditary PGL/PCC Syndromes Attributed to Pathogenic Variants in Gene 3Proportion of Pathogenic Variants 4 Detectable by Method
Sequence analysis 3, 5Gene-targeted deletion/duplication analysis 3, 6
MAX ~4%~90%~10%
SDHA ~4%~98%1 reported
SDHAF2 ~1%~100%None reported
SDHB 50%-55% 7~85%-95%~5%-15%
SDHC ~8%~85%~15%
SDHD ~20%-25% 890%-95%5%-10%
TMEM127 ~5% 3~100%None reported
Unknown 9NA

PGL = paraganglioma; PCC = pheochromocytoma

1.

Genes are listed in alphabetic order.

2.
3.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020]

4.

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

5.

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.

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. Due to pseudogenes, many labs do not perform SDHA deletion/duplication analysis.

7.

An SDHB pathogenic variant is identified in 24%-44% of individuals with chest, abdomen, or pelvic PGL/PCCs [Amar et al 2005, Burnichon et al 2009] and 12%-20% of individuals with HNPGLs [Baysal et al 2002, Burnichon et al 2009].

8.

An SDHD pathogenic variant is identified in 15% of individuals with chest, abdomen, or pelvic PGL/PCCs [Amar et al 2005, Burnichon et al 2009] and 40%-50% of individuals with HNGPLs [Baysal et al 2002, Burnichon et al 2009].

9.

This table includes the core genes associated with hereditary paraganglioma-pheochromocytoma syndromes. FH and MDH2 are likely susceptibility genes (see Differential Diagnosis). EGLN1, EGLN2, EPAS1, KIF1B, KMT2D, and additional genes have been reported to be associated with hereditary PGL/PCC; their clinical significance is as yet unclear.

From: Hereditary Paraganglioma-Pheochromocytoma Syndromes

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