PGL4
MCID: PRG021
MIFTS: 38

Paragangliomas 4 (PGL4)

Categories: Cancer diseases, Ear diseases, Endocrine diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Paragangliomas 4

MalaCards integrated aliases for Paragangliomas 4:

Name: Paragangliomas 4 57 20 72 29 13 6 70
Pgl4 57 20 72
Carotid Body Tumors and Multiple Extraadrenal Pheochromocytomas 57 72
Paragangliomas, Hereditary Extraadrenal 57 20
Pheochromocytoma, Familial Extraadrenal 57 20
Paraganglioma, Familial Malignant 57 20
Sdhb-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome 20
Pheochromocytoma, Extraadrenal, and Cervical Paraganglioma 57
Pheochromocytoma, Extraadrenal and Cervical Paraganglioma 20
Pheochromocytoma Extraadrenal and Cervical Paraganglioma 72
Paragangliomas Hereditary Extraadrenal 72
Pheochromocytoma Familial Extraadrenal 72
Familial Chromaffin Paraganglioma 4 72
Paraganglioma Familial Malignant 72
Paragangliomas, Type 4 39

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal dominant

Miscellaneous:
adult onset (mean 30 years, range 10-65 years)
incomplete penetrance (range 13% to 77% by 50 years of age)
signs and symptoms depend on tumor location and activity
patients may have head and neck paragangliomas only, adrenal or extraadrenal pheochromocytomas only, or both
see also pgl1


HPO:

31
paragangliomas 4:
Inheritance autosomal dominant inheritance
Onset and clinical course adult onset incomplete penetrance


Classifications:



Summaries for Paragangliomas 4

UniProtKB/Swiss-Prot : 72 Paragangliomas 4: A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion. Paragangliomas can develop at various body sites, including the head, neck, thorax and abdomen. Most commonly, they are located in the head and neck region, specifically at the carotid bifurcation, the jugular foramen, the vagal nerve, and in the middle ear.

MalaCards based summary : Paragangliomas 4, also known as pgl4, is related to hereditary paraganglioma-pheochromocytoma syndromes and neuroblastoma 1. An important gene associated with Paragangliomas 4 is SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B). Affiliated tissues include liver, lung and pituitary, and related phenotypes are neuroblastoma and gastrointestinal stroma tumor

More information from OMIM: 115310 PS168000

Related Diseases for Paragangliomas 4

Graphical network of the top 20 diseases related to Paragangliomas 4:



Diseases related to Paragangliomas 4

Symptoms & Phenotypes for Paragangliomas 4

Human phenotypes related to Paragangliomas 4:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 neuroblastoma 31 occasional (7.5%) HP:0003006
2 gastrointestinal stroma tumor 31 occasional (7.5%) HP:0100723
3 paraganglioma of head and neck 31 occasional (7.5%) HP:0002864
4 hyperhidrosis 31 HP:0000975
5 cranial nerve paralysis 31 HP:0006824
6 renal cell carcinoma 31 HP:0005584
7 tachycardia 31 HP:0001649
8 elevated urinary catecholamines 31 HP:0011976
9 palpitations 31 HP:0001962
10 recurrent paroxysmal headache 31 HP:0002331
11 hypertension associated with pheochromocytoma 31 HP:0002640
12 adrenal pheochromocytoma 31 HP:0006748
13 extraadrenal pheochromocytoma 31 HP:0006737
14 episodic paroxysmal anxiety 31 HP:0000740
15 pulsatile tinnitus 31 HP:0008629
16 glomus jugular tumor 31 HP:0003001
17 chemodectoma 31 HP:0030074

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Ears:
pulsatile tinnitus (tympanic paraganglioma)

Cardiovascular Vascular:
hypertension (with pheochromocytoma)

Neurologic Central Nervous System:
headache (with pheochromocytoma)
cranial nerve palsies can arise with head and neck paragangliomas

Neoplasia:
paragangliomas
multiple tumors in 28% of patients
paragangliomas, head and neck (31%)
chemodectomas
carotid body tumors
more
Cardiovascular Heart:
palpitations (with pheochromocytoma)
tachycardia (with pheochromocytoma)

Skin Nails Hair Skin:
diaphoresis (with pheochromocytoma)

Neurologic Behavioral Psychiatric Manifestations:
anxiety (with pheochromocytoma)

Laboratory Abnormalities:
increased urinary catecholamines (with pheochromocytoma)

Clinical features from OMIM®:

115310 (Updated 05-Apr-2021)

Drugs & Therapeutics for Paragangliomas 4

Search Clinical Trials , NIH Clinical Center for Paragangliomas 4

Genetic Tests for Paragangliomas 4

Genetic tests related to Paragangliomas 4:

# Genetic test Affiliating Genes
1 Paragangliomas 4 29 SDHB

Anatomical Context for Paragangliomas 4

MalaCards organs/tissues related to Paragangliomas 4:

40
Liver, Lung, Pituitary, Spinal Cord, Kidney, Thyroid

Publications for Paragangliomas 4

Articles related to Paragangliomas 4:

(show top 50) (show all 201)
# Title Authors PMID Year
1
Low penetrance of paraganglioma and pheochromocytoma in an extended kindred with a germline SDHB exon 3 deletion. 6 57
25827221 2016
2
High prevalence of founder mutations of the succinate dehydrogenase genes in the Netherlands. 6 57
21348866 2012
3
Paraganglioma, neuroblastoma, and a SDHB mutation: Resolution of a 30-year-old mystery. 57 6
20503330 2010
4
Molecular characterisation of a common SDHB deletion in paraganglioma patients. 57 6
18057081 2008
5
High frequency of germline succinate dehydrogenase mutations in sporadic cervical paragangliomas in northern Spain: mitochondrial succinate dehydrogenase structure-function relationships and clinical-pathological correlations. 6 57
17848412 2007
6
Succinate dehydrogenase B gene mutations predict survival in patients with malignant pheochromocytomas or paragangliomas. 6 57
17652212 2007
7
Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas. 57 6
17200167 2007
8
Clinical presentation and penetrance of pheochromocytoma/paraganglioma syndromes. 6 57
16317055 2006
9
Distinct clinical features of paraganglioma syndromes associated with SDHB and SDHD gene mutations. 57 6
15328326 2004
10
Early-onset renal cell carcinoma as a novel extraparaganglial component of SDHB-associated heritable paraganglioma. 6 57
14685938 2004
11
Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene. 57 6
12213855 2002
12
Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. 57 6
11404820 2001
13
A family with hereditary extra-adrenal paragangliomas without evidence for mutations in the von Hippel-Lindau disease or ret genes. 6 57
9509062 1998
14
Neuroblastoma, pheochromocytoma, and renal cell carcinoma. Occurrence in a single patient. 6 57
490809 1979
15
The phenotype of SDHB germline mutation carriers: a nationwide study. 6 61
28490599 2017
16
Four generations of SDHB-related disease: complexities in management. 61 6
27896548 2017
17
15 YEARS OF PARAGANGLIOMA: Clinical manifestations of paraganglioma syndromes types 1-5. 61 6
26273102 2015
18
Renal tumors associated with germline SDHB mutation show distinctive morphology. 61 6
21934479 2011
19
An analysis of surveillance screening for SDHB-related disease in childhood and adolescence. 6
30694796 2019
20
Tumour risks and genotype-phenotype correlations associated with germline variants in succinate dehydrogenase subunit genes SDHB, SDHC and SDHD. 6
29386252 2018
21
Nationwide study of patients with head and neck paragangliomas carrying SDHB germline mutations. 6
29951630 2018
22
Analysis of SDHAF3 in familial and sporadic pheochromocytoma and paraganglioma. 6
28738844 2017
23
Succinate Dehydrogenase B (SDHB)-Associated Bladder Paragangliomas. 6
27542510 2017
24
Leukoencephalopathy due to Complex II Deficiency and Bi-Allelic SDHB Mutations: Further Cases and Implications for Genetic Counselling. 6
27604842 2017
25
Novel SDHB and TMEM127 Mutations in Patients with Pheochromocytoma/Paraganglioma Syndrome. 6
26960314 2016
26
Germline mutations and genotype-phenotype correlation in Asian Indian patients with pheochromocytoma and paraganglioma. 6
27539324 2016
27
Cardiac Paraganglioma Arising From the Right Atrioventricular Groove in a Paraganglioma-Pheochromocytoma Family Syndrome With Evidence of SDHB Gene Mutation: An Unusual Presentation. 6
27549546 2016
28
Mediastinal paragangliomas related to SDHx gene mutations. 6
27785149 2016
29
Whole exome sequencing in patients with white matter abnormalities. 6
27159321 2016
30
Magnetic resonance imaging spectrum of succinate dehydrogenase-related infantile leukoencephalopathy. 6
26642834 2016
31
SDHB-Deficient Cancers: The Role of Mutations That Impair Iron Sulfur Cluster Delivery. 6
26719882 2016
32
Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA. 6
26556299 2016
33
Mitochondrial leukoencephalopathy and complex II deficiency associated with a recessive SDHB mutation with reduced penetrance. 6
26925370 2015
34
Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum. 6
26259135 2015
35
Genetics of Apparently Sporadic Pheochromocytoma and Paraganglioma in a Chinese Population. 6
26267327 2015
36
Superiority of [68Ga]-DOTATATE PET/CT to Other Functional Imaging Modalities in the Localization of SDHB-Associated Metastatic Pheochromocytoma and Paraganglioma. 6
25873086 2015
37
Structural and functional consequences of succinate dehydrogenase subunit B mutations. 6
25972245 2015
38
Additive effect of nuclear and mitochondrial mutations in a patient with mitochondrial encephalomyopathy. 6
25736212 2015
39
Pituitary adenoma with paraganglioma/pheochromocytoma (3PAs) and succinate dehydrogenase defects in humans and mice. 6
25695889 2015
40
Association of urinary bladder paragangliomas with germline mutations in the SDHB and VHL genes. 6
25683602 2015
41
[Intrapericardical paraganglioma associated with mutation in succinate dehydrogenase enzyme gene]. 6
24939699 2015
42
Mutations seen among patients with pheochromocytoma and paraganglioma at a referral center from India. 6
24977658 2015
43
Lack of utility of SDHB mutation testing in adrenergic metastatic phaeochromocytoma. 6
25371406 2015
44
SDHD immunohistochemistry: a new tool to validate SDHx mutations in pheochromocytoma/paraganglioma. 6
25405498 2015
45
Paraganglioma Presenting as Postpartum Fever of Unknown Origin. 6
26236513 2015
46
Succinate dehydrogenase (SDH)-deficient renal carcinoma: a morphologically distinct entity: a clinicopathologic series of 36 tumors from 27 patients. 6
25025441 2014
47
Phenotype of SDHB mutation carriers in the Netherlands. 6
25047027 2014
48
Germline mutations and genotype-phenotype correlations in patients with apparently sporadic pheochromocytoma/paraganglioma in Korea. 6
24134185 2014
49
Simultaneous KIT mutation and succinate dehydrogenase (SDH) deficiency in a patient with a gastrointestinal stromal tumour and Carney-Stratakis syndrome: a case report. 6
25130709 2014
50
Clinical exome sequencing for genetic identification of rare Mendelian disorders. 6
25326637 2014

Variations for Paragangliomas 4

ClinVar genetic disease variations for Paragangliomas 4:

6 (show top 50) (show all 548)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 SDHB NM_003000.2(SDHB):c.590C>G (p.Pro197Arg) SNV Pathogenic 12779 rs74315367 GRCh37: 1:17350520-17350520
GRCh38: 1:17024025-17024025
2 SDHB NM_003000.2(SDHB):c.(?_-151)_(72+1_73-1)del Deletion Pathogenic 12784 GRCh37:
GRCh38:
3 SDHB NC_000001.10:g.17375249_17390927del15679 Deletion Pathogenic 18455 GRCh37: 1:17375249-17390927
GRCh38: 1:17048754-17064432
4 overlap with 2 genes NC_000001.10:g.17376556_17396932del20377 Deletion Pathogenic 18456 GRCh37: 1:17376556-17396932
GRCh38: 1:17050061-17070437
5 SDHB NM_003000.2(SDHB):c.-151_*159del Deletion Pathogenic 239419 GRCh37: 1:17345217-17380665
GRCh38: 1:17018722-17054170
6 SDHB NM_003000.2(SDHB):c.271A>T (p.Arg91Ter) SNV Pathogenic 239427 rs878854575 GRCh37: 1:17359570-17359570
GRCh38: 1:17033075-17033075
7 SDHB NM_003000.2(SDHB):c.126del (p.Phe42fs) Deletion Pathogenic 239421 rs878854572 GRCh37: 1:17371330-17371330
GRCh38: 1:17044835-17044835
8 SDHB NM_003000.2(SDHB):c.374C>G (p.Ser125Ter) SNV Pathogenic 412455 rs786203506 GRCh37: 1:17355144-17355144
GRCh38: 1:17028649-17028649
9 SDHB NM_003000.2(SDHB):c.602G>A (p.Trp201Ter) SNV Pathogenic 412470 rs1060503759 GRCh37: 1:17350508-17350508
GRCh38: 1:17024013-17024013
10 SDHB NM_003000.2(SDHB):c.441T>G (p.Tyr147Ter) SNV Pathogenic 412476 rs1060503763 GRCh37: 1:17354343-17354343
GRCh38: 1:17027848-17027848
11 SDHB NM_003000.2(SDHB):c.499A>T (p.Lys167Ter) SNV Pathogenic 412456 rs1060503753 GRCh37: 1:17354285-17354285
GRCh38: 1:17027790-17027790
12 SDHB NM_003000.2(SDHB):c.22_23delTC Microsatellite Pathogenic 412488 rs1060503767 GRCh37: 1:17380492-17380493
GRCh38: 1:17053997-17053998
13 SDHB NC_000001.11:g.(?_17044761)_(17044888_?)del Deletion Pathogenic 417581 GRCh37: 1:17371256-17371383
GRCh38: 1:17044761-17044888
14 SDHB NM_003000.2(SDHB):c.620_621del (p.Leu207fs) Deletion Pathogenic 412454 rs1060503752 GRCh37: 1:17350489-17350490
GRCh38: 1:17023994-17023995
15 SDHB NM_003000.2(SDHB):c.141G>A (p.Trp47Ter) SNV Pathogenic 412474 rs1060503762 GRCh37: 1:17371315-17371315
GRCh38: 1:17044820-17044820
16 SDHB NM_003000.2(SDHB):c.221A>C (p.Asp74Ala) SNV Pathogenic 230694 rs876658713 GRCh37: 1:17359620-17359620
GRCh38: 1:17033125-17033125
17 SDHB NM_003000.2(SDHB):c.717dup (p.Leu240fs) Duplication Pathogenic 412481 rs1060503764 GRCh37: 1:17349150-17349151
GRCh38: 1:17022655-17022656
18 SDHB NM_003000.2(SDHB):c.329_330CT[1] (p.Leu111fs) Microsatellite Pathogenic 412453 rs1060503751 GRCh37: 1:17355186-17355187
GRCh38: 1:17028691-17028692
19 SDHB NM_003000.2(SDHB):c.502C>T (p.Gln168Ter) SNV Pathogenic 468234 rs1553177677 GRCh37: 1:17354282-17354282
GRCh38: 1:17027787-17027787
20 SDHB NM_003000.2(SDHB):c.697A>T (p.Lys233Ter) SNV Pathogenic 468235 rs1553177285 GRCh37: 1:17349171-17349171
GRCh38: 1:17022676-17022676
21 SDHB NM_003000.2(SDHB):c.200+5G>C SNV Pathogenic 440259 rs1553178726 GRCh37: 1:17371251-17371251
GRCh38: 1:17044756-17044756
22 SDHB NC_000001.11:g.(?_17018875)_(17044894_?)del Deletion Pathogenic 468230 GRCh37: 1:17345370-17371389
GRCh38: 1:17018875-17044894
23 SDHB NC_000001.10:g.(?_17380437)_(17380520_?)del Deletion Pathogenic 468232 GRCh37: 1:17380437-17380520
GRCh38:
24 SDHB NM_003000.2(SDHB):c.591del (p.Ser198fs) Deletion Pathogenic 412462 rs1060503757 GRCh37: 1:17350519-17350519
GRCh38: 1:17024024-17024024
25 SDHB NM_003000.2(SDHB):c.685_686insCGCTTCACAGAGG (p.Glu229fs) Insertion Pathogenic 468238 rs1209914140 GRCh37: 1:17349182-17349183
GRCh38: 1:17022687-17022688
26 SDHB NM_003000.3(SDHB):c.343C>T (p.Arg115Ter) SNV Pathogenic 197210 rs751000085 GRCh37: 1:17355175-17355175
GRCh38: 1:17028680-17028680
27 SDHB NM_003000.2(SDHB):c.190del (p.Asp64fs) Deletion Pathogenic 468233 rs1553178729 GRCh37: 1:17371266-17371266
GRCh38: 1:17044771-17044771
28 SDHB NM_003000.2(SDHB):c.505C>T (p.Gln169Ter) SNV Pathogenic 528736 rs1553177676 GRCh37: 1:17354279-17354279
GRCh38: 1:17027784-17027784
29 SDHB NM_003000.2(SDHB):c.608del (p.Gly203fs) Deletion Pathogenic 528737 rs1553177436 GRCh37: 1:17350502-17350502
GRCh38: 1:17024007-17024007
30 SDHB NM_003000.2(SDHB):c.112del (p.Arg38fs) Deletion Pathogenic 528741 rs398123690 GRCh37: 1:17371344-17371344
GRCh38: 1:17044849-17044849
31 SDHB NM_003000.2(SDHB):c.491del (p.Gln164fs) Deletion Pathogenic 528750 rs1553177678 GRCh37: 1:17354293-17354293
GRCh38: 1:17027798-17027798
32 SDHB NM_003000.2(SDHB):c.286+1G>A SNV Pathogenic 183757 rs786201063 GRCh37: 1:17359554-17359554
GRCh38: 1:17033059-17033059
33 SDHB NM_003000.2(SDHB):c.287G>A (p.Gly96Asp) SNV Pathogenic 428916 rs778952116 GRCh37: 1:17355231-17355231
GRCh38: 1:17028736-17028736
34 SDHB NC_000001.11:g.(?_17033054)_(17033151_?)del Deletion Pathogenic 528762 GRCh37: 1:17359549-17359646
GRCh38: 1:17033054-17033151
35 SDHB NM_003000.2(SDHB):c.399dup (p.Tyr134fs) Duplication Pathogenic 579501 rs1557741425 GRCh37: 1:17355118-17355119
GRCh38: 1:17028623-17028624
36 SDHB NC_000001.11:g.(?_17033050)_(17033155_?)del Deletion Pathogenic 583569 GRCh37: 1:17359545-17359650
GRCh38: 1:17033050-17033155
37 SDHB NC_000001.11:g.(?_17053938)_(17054029_?)del Deletion Pathogenic 583582 GRCh37: 1:17380433-17380524
GRCh38: 1:17053938-17054029
38 SDHB NC_000001.11:g.(?_17018875)_(17033151_?)del Deletion Pathogenic 583909 GRCh37: 1:17345370-17359646
GRCh38: 1:17018875-17033151
39 overlap with 2 genes NC_000001.11:g.(?_17018881)_(17071491_?)del Deletion Pathogenic 584021 GRCh37: 1:17345376-17397986
GRCh38: 1:17018881-17071491
40 SDHB NM_003000.2(SDHB):c.148_151dup (p.Lys51fs) Duplication Pathogenic 642012 rs1570958022 GRCh37: 1:17371304-17371305
GRCh38: 1:17044809-17044810
41 SDHB NM_003000.2(SDHB):c.609_622dup (p.Gly208fs) Duplication Pathogenic 642173 rs1570945796 GRCh37: 1:17350487-17350488
GRCh38: 1:17023992-17023993
42 SDHB NM_003000.2(SDHB):c.683_684delAG Microsatellite Pathogenic 438428 rs762812025 GRCh37: 1:17349184-17349185
GRCh38: 1:17022689-17022690
43 SDHB NC_000001.11:g.(?_17018871)_(17018968_?)del Deletion Pathogenic 649062 GRCh37: 1:17345366-17345463
GRCh38: 1:17018871-17018968
44 SDHB NC_000001.11:g.(?_17044751)_(17044898_?)del Deletion Pathogenic 649629 GRCh37: 1:17371246-17371393
GRCh38: 1:17044751-17044898
45 SDHB NM_003000.2(SDHB):c.136C>G (p.Arg46Gly) SNV Pathogenic 12785 rs74315370 GRCh37: 1:17371320-17371320
GRCh38: 1:17044825-17044825
46 SDHB NC_000001.11:g.(?_17018871)_(17054029_?)del Deletion Pathogenic 646398 GRCh37: 1:17345366-17380524
GRCh38: 1:17018871-17054029
47 SDHB NM_003000.2(SDHB):c.311delinsGG (p.Asn104fs) Indel Pathogenic 184177 rs786201316 GRCh37: 1:17355207-17355207
GRCh38: 1:17028712-17028712
48 SDHB NM_003000.2(SDHB):c.143_144dup (p.Pro49fs) Duplication Pathogenic 656223 rs1570958038 GRCh37: 1:17371311-17371312
GRCh38: 1:17044816-17044817
49 SDHB NM_003000.2(SDHB):c.70C>T (p.Gln24Ter) SNV Pathogenic 664893 rs1570963430 GRCh37: 1:17380445-17380445
GRCh38: 1:17053950-17053950
50 SDHB NM_003000.3(SDHB):c.63dup (p.Cys22fs) Duplication Pathogenic 658395 rs1570963451 GRCh37: 1:17380451-17380452
GRCh38: 1:17053956-17053957

UniProtKB/Swiss-Prot genetic disease variations for Paragangliomas 4:

72
# Symbol AA change Variation ID SNP ID
1 SDHB p.Pro197Arg VAR_017868 rs74315367
2 SDHB p.Arg242His VAR_017869 rs74315368
3 SDHB p.Pro131Arg VAR_018518
4 SDHB p.His132Pro VAR_037621 rs74315372
5 SDHB p.Arg46Gln VAR_054377 rs772551056

Expression for Paragangliomas 4

Search GEO for disease gene expression data for Paragangliomas 4.

Pathways for Paragangliomas 4

GO Terms for Paragangliomas 4

Sources for Paragangliomas 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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