Table 2.
Germline mutations in the SDHB gene in the index cases
| Exon/Intron | SDHB mutation (cDNA nucleotide) | SDHB mutation/protein change | Type | Pathogenicity* | Index cases | Carriers+ | Carriers with disease | Types of PHEO/PGL in families |
|---|---|---|---|---|---|---|---|---|
| 1 – 8 | c.1 – c.843+del | Exon 1–8 deletion | large deletion | AF | 2 | 2 | 1 | EA-S |
| 1 | c.1-16418_73-5173del | Exon 1 deletion | large deletion | AF | 4 | 27 | 8 | EA-S, A, EA-P |
| 1 | c.1A>T | p.Met1Leu | missense | AF | 1 | 0 | 0 | EA-P |
| 1 | c.26T>A | p.Leu9X | nonsense | AF | 1 | 2 | 0 | EA-S |
| 1 | c.32G>A | p.Arg11His | missense | VUS | 1 | 1 | 0 | A |
| IVS 1 | c.72+1G>T | IVS1+1G>T | splice site | AF | 8 | 19 | 1 | EA-S, EA-P, A |
| IVS 1 | c.73-9A>G | IVS1–9A>G | splice site | VUS | 1 | 0 | 1 | EA-S |
| 2 | c.79C>A | p.Arg27X | nonsense | AF | 1 | 12 | 0 | EA-S |
| 2 | c.136C>T | p.Arg46X | nonsense | AF | 10 | 10 | 0 | EA-S, A, EA-P |
| 2 | c.137G>A | p.Arg46Gln | missense | AF | 4 | 14 | 2 | EA-S |
| 2 | c.183T>G | p.Tyr61X | nonsense | AF | 1 | 1 | 0 | A |
| 3 | c.268C>T | p.Arg90X | nonsense | AF | 5 | 43 | 9 | EA-S, EA-P |
| 3 | c.271A>T | p.Arg91X | nonsense | AF | 1 | 0 | 0 | EA-S |
| 3 | c.274T>C | p.Ser92Pro | missense | VUS | 1 | 0 | 0 | EA-S |
| 3 | c.275C>A | p.Ser92X | nonsense | 1 | 0 | 0 | EA-S | |
| 3 | c.277T>C | p.Cys93Arg | missense | likely AF | 1 | 0 | 0 | A |
| 3 | c.286G>A | p.Gly96Ser | missense | likely AF | 1 | 1 | 0 | EA-P |
| IVS 3 | c.286+1G>A | IVS3+1G>A | splice site | likely AF | 3 | 2 | 0 | EA-S, EA-P |
| IVS 3 | c.286+2T>A | IVS3+2T>A | splice site | AF | 3 | 0 | N/A | EA-S |
| IVS 3 | c.287-1G>C | IVS3-1G>C | splice site | likely AF | 2 | 6 | 1 | EA-S, EA-P |
| IVS 3 | c.287-3C>G | IVS3-3C>G | splice site | AF | 1 | 0 | N/A | EA-P |
| 4 | c.287G>A | p.Gly96Asp | missense | likely AF | 1 | 0 | 0 | EA-S |
| 4 | c.330_331del | p.Leu111SerfsX7 | frameshift | AF | 1 | 3 | 1 | A |
| 4 | c.343C>T | p.Arg115X | nonsense | AF | 1 | 0 | 0 | EA-S |
| 4 | c.348_352het_del GATTG | p.Ile117HisfsX5 | frameshift | VUS | 1 | 1 | 0 | A |
| 4 | c.369_370insA | p.Val124SerfsX39 | frameshift | AF | 1 | 0 | 0 | EA-S |
| 4 | c.380T>G | p.Ile127Ser | missense | likely AF | 5 | 28 | 5 | EA-S, A, EA, P |
| 4 | c.392delC | p.Pro131HisfsX5 | frameshift | AF | 1 | 0 | 0 | A, EA-S |
| 4 | c.418G>T | p.Val140Phe | missense | AF | 9 | 16 | 5 | EA-S, EA-P, A |
| 5 | c.445-447delCAinsGGTATCT | p.Gln149LeufsX159 | frameshift | VUS | 1 | 1 | 0 | EA-S |
| 5 | c.445C>T | p.Gln149X | nonsense | AF | 1 | 0 | 0 | A |
| 5 | c.487T>C | p.Ser163Pro | missense | VUS | 1 | 0 | 0 | EA-S |
| 5 | c.490C>T | p.Gln164X | nonsense | AF | 1 | 2 | 0 | EA-S |
| 5 | c.540G>A | p.Leu180Leu | splice site | VUS | 1 | 1 | 1 | EA-S |
| IVS 5 | c.541-2A>G | IVS5-2A>G | splice site | AF | 3 | 5 | 3 | A, EA-S, EA-P |
| 6 | c.574T>C | p.Cys192Arg | missense | AF | 1 | 0 | 0 | EA-S |
| 6 | c.575G>A | p.Cys192Tyr | missense | AF | 1 | 6 | 0 | EA-P |
| 6 | c.587G>A | p.Cys196Tyr | missense | AF | 3 | 1 | 1 | EA-S, A |
| 6 | c.590C>G | p.Pro197Arg | missense | AF | 1 | 1 | 0 | EA-S |
| 6 | c.600G>T | p.Trp200Cys | missense | AF | 2 | 3 | 0 | EA-S |
| 6 | c.642G>C | p.Gln214His | missense | VUS | 1 | 0 | 0 | A |
| IVS 6 | c.642+1G>A | IVS6+1G>A | splice site | AF | 2 | 4 | 1 | EA-S |
| 7 | c.683_684delAG | p.Glu228GlyfsX27 | frameshift | AF | 1 | 0 | 0 | EA-S |
| 7 | c.688C>T | p.Arg230Cys | missense | AF | 3 | 5 | 1 | EA-S, EA-P |
| 7 | c.689G>A | p.Arg230His | missense | AF | 3 | 9 | 0 | A, EA-S, EA-P |
| 7 | c.725G>A | p.Arg242His | missense | AF | 1 | 0 | 0 | EA-S |
| 7 | c.746G>T | p.Cys249Phe | missense | VUS | 1 | 0 | 0 | A |
| 7 | c.761insC | p.Pro254fsX255 | frameshift | VUS | 1 | 0 | 0 | EA-S |
*
As reported by LOVD and NCBI ClinVar databases
+
Number of carriers out of 241 included in the study, excluding the index cases
Abbreviations: A, adrenal; AF, affects function; EA-S, extra-adrenal sympathetic; EA-P, extra-adrenal parasympathetic; SNV, Single nucleotide variant; VUS, variant of unknown significance