PGL4
MCID: PRG021
MIFTS: 31

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 58 54 76 30 13 6 74
Pgl4 58 54 76
Carotid Body Tumors and Multiple Extraadrenal Pheochromocytomas 58 76
Paragangliomas, Hereditary Extraadrenal 58 54
Pheochromocytoma, Familial Extraadrenal 58 54
Paraganglioma, Familial Malignant 58 54
Sdhb-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome 54
Pheochromocytoma, Extraadrenal, and Cervical Paraganglioma 58
Pheochromocytoma, Extraadrenal and Cervical Paraganglioma 54
Pheochromocytoma Extraadrenal and Cervical Paraganglioma 76
Paragangliomas Hereditary Extraadrenal 76
Pheochromocytoma Familial Extraadrenal 76
Familial Chromaffin Paraganglioma 4 76
Paraganglioma Familial Malignant 76
Paragangliomas, Type 4 41

Characteristics:

OMIM:

58
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:

33
paragangliomas 4:
Onset and clinical course adult onset incomplete penetrance
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Paragangliomas 4

UniProtKB/Swiss-Prot : 76 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 adrenal gland, testes and thyroid, and related phenotypes are neuroblastoma and gastrointestinal stroma tumor

Description from OMIM: 115310

Related Diseases for Paragangliomas 4

Diseases in the Paraganglioma family:

Paragangliomas 4 Paragangliomas 1
Paragangliomas 2 Paragangliomas 3
Paragangliomas 5 Nonsyndromic Paraganglioma

Diseases related to Paragangliomas 4 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary paraganglioma-pheochromocytoma syndromes 11.3
2 neuroblastoma 1 11.2
3 pheochromocytoma 10.4
4 adrenal gland pheochromocytoma 10.4
5 paragangliomas 3 10.1
6 paraganglioma 10.1

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:

33 (show all 17)
# Description HPO Frequency HPO Source Accession
1 neuroblastoma 33 occasional (7.5%) HP:0003006
2 gastrointestinal stroma tumor 33 occasional (7.5%) HP:0100723
3 paraganglioma of head and neck 33 occasional (7.5%) HP:0002864
4 hyperhidrosis 33 HP:0000975
5 cranial nerve paralysis 33 HP:0006824
6 renal cell carcinoma 33 HP:0005584
7 tachycardia 33 HP:0001649
8 elevated urinary catecholamines 33 HP:0011976
9 palpitations 33 HP:0001962
10 recurrent paroxysmal headache 33 HP:0002331
11 extraadrenal pheochromocytoma 33 HP:0006737
12 adrenal pheochromocytoma 33 HP:0006748
13 episodic paroxysmal anxiety 33 HP:0000740
14 hypertension associated with pheochromocytoma 33 HP:0002640
15 pulsatile tinnitus 33 HP:0008629
16 glomus jugular tumor 33 HP:0003001
17 chemodectoma 33 HP:0030074

Symptoms via clinical synopsis from OMIM:

58
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

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 30 SDHB

Anatomical Context for Paragangliomas 4

MalaCards organs/tissues related to Paragangliomas 4:

42
Adrenal Gland, Testes, Thyroid

Publications for Paragangliomas 4

Articles related to Paragangliomas 4:

(show all 29)
# Title Authors Year
1
Treatment responses to antiangiogenetic therapy and chemotherapy in nonsecreting paraganglioma (PGL4) of urinary bladder with SDHB mutation: A case report. ( 30045248 )
2018
2
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. ( 27854360 )
2017
3
Low penetrance of paraganglioma and pheochromocytoma in an extended kindred with a germline SDHB exon 3 deletion. ( 25827221 )
2016
4
ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing. ( 25356965 )
2015
5
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment. ( 25394175 )
2015
6
Pheochromocytoma in a Twelve-Year-Old Girl with SDHB-Related Hereditary Paraganglioma-Pheochromocytoma Syndrome. ( 25215250 )
2014
7
Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. ( 24893135 )
2014
8
ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. ( 23788249 )
2013
9
Canadian guideline on genetic screening for hereditary renal cell cancers. ( 24319509 )
2013
10
High prevalence of founder mutations of the succinate dehydrogenase genes in the Netherlands. ( 21348866 )
2012
11
Succinate dehydrogenase gene variants and their role in Cowden syndrome. ( 21565294 )
2011
12
Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. ( 21173220 )
2011
13
Endocrine cancer predisposition syndromes: hereditary paraganglioma, multiple endocrine neoplasia type 1, multiple endocrine neoplasia type 2, and hereditary thyroid cancer. ( 20816580 )
2010
14
Paraganglioma, neuroblastoma, and a SDHB mutation: Resolution of a 30-year-old mystery. ( 20503330 )
2010
15
Evaluation of anti-Wnt/β-catenin signaling agents by pGL4-TOP transfected stable cells with a luciferase reporter system. ( 20835687 )
2010
16
American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. ( 20065170 )
2010
17
Penetrance and clinical consequences of a gross SDHB deletion in a large family. ( 19389109 )
2009
18
Molecular characterisation of a common SDHB deletion in paraganglioma patients. ( 18057081 )
2008
19
Quantification of PRL/Stat5 signaling with a novel pGL4-CISH reporter. ( 18254957 )
2008
20
Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. ( 16405730 )
2006
21
Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: a possible hot spot? ( 16258955 )
2006
22
Comparison of the responsiveness of the pGL3 and pGL4 luciferase reporter vectors to steroid hormones. ( 16116793 )
2005
23
Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma. ( 15531530 )
2004
24
A novel succinate dehydrogenase subunit B gene mutation, H132P, causes familial malignant sympathetic extraadrenal paragangliomas. ( 14715873 )
2004
25
Familial malignant catecholamine-secreting paraganglioma with prolonged survival associated with mutation in the succinate dehydrogenase B gene. ( 12213855 )
2002
26
Germ-line mutations in nonsyndromic pheochromocytoma. ( 12000816 )
2002
27
Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma. ( 11404820 )
2001
28
A family with hereditary extra-adrenal paragangliomas without evidence for mutations in the von Hippel-Lindau disease or ret genes. ( 9509062 )
1998
29
Neuroblastoma, pheochromocytoma, and renal cell carcinoma. Occurrence in a single patient. ( 490809 )
1979

Variations for Paragangliomas 4

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

76
# 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

ClinVar genetic disease variations for Paragangliomas 4:

6 (show top 50) (show all 557)
# Gene Variation Type Significance SNP ID Assembly Location
1 SDHB NM_003000.2(SDHB): c.268C> T (p.Arg90Ter) single nucleotide variant Pathogenic rs74315366 GRCh37 Chromosome 1, 17359573: 17359573
2 SDHB NM_003000.2(SDHB): c.268C> T (p.Arg90Ter) single nucleotide variant Pathogenic rs74315366 GRCh38 Chromosome 1, 17033078: 17033078
3 SDHB NM_003000.2(SDHB): c.590C> G (p.Pro197Arg) single nucleotide variant Likely pathogenic rs74315367 GRCh37 Chromosome 1, 17350520: 17350520
4 SDHB NM_003000.2(SDHB): c.590C> G (p.Pro197Arg) single nucleotide variant Likely pathogenic rs74315367 GRCh38 Chromosome 1, 17024025: 17024025
5 SDHB NM_003000.2(SDHB): c.725G> A (p.Arg242His) single nucleotide variant Pathogenic rs74315368 GRCh37 Chromosome 1, 17349143: 17349143
6 SDHB NM_003000.2(SDHB): c.725G> A (p.Arg242His) single nucleotide variant Pathogenic rs74315368 GRCh38 Chromosome 1, 17022648: 17022648
7 SDHB NM_003000.2(SDHB): c.716_719delCTCT (p.Ser239Tyrfs) deletion Pathogenic rs587781266 GRCh38 Chromosome 1, 17022654: 17022657
8 SDHB NM_003000.2(SDHB): c.716_719delCTCT (p.Ser239Tyrfs) deletion Pathogenic rs587781266 GRCh37 Chromosome 1, 17349149: 17349152
9 SDHB NM_003000.2(SDHB): c.79C> T (p.Arg27Ter) single nucleotide variant Pathogenic rs74315369 GRCh37 Chromosome 1, 17371377: 17371377
10 SDHB NM_003000.2(SDHB): c.79C> T (p.Arg27Ter) single nucleotide variant Pathogenic rs74315369 GRCh38 Chromosome 1, 17044882: 17044882
11 SDHB NM_003000.2(SDHB): c.(?_-151)_(72+1_73-1)del deletion Pathogenic
12 SDHB NM_003000.2(SDHB): c.395A> C (p.His132Pro) single nucleotide variant Pathogenic rs74315372 GRCh37 Chromosome 1, 17355123: 17355123
13 SDHB NM_003000.2(SDHB): c.395A> C (p.His132Pro) single nucleotide variant Pathogenic rs74315372 GRCh38 Chromosome 1, 17028628: 17028628
14 SDHB NM_003000.2(SDHB): c.8C> G (p.Ala3Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs11203289 GRCh37 Chromosome 1, 17380507: 17380507
15 SDHB NM_003000.2(SDHB): c.8C> G (p.Ala3Gly) single nucleotide variant Conflicting interpretations of pathogenicity rs11203289 GRCh38 Chromosome 1, 17054012: 17054012
16 SDHB NM_003000.2(SDHB): c.487T> C (p.Ser163Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs33927012 GRCh37 Chromosome 1, 17354297: 17354297
17 SDHB NM_003000.2(SDHB): c.487T> C (p.Ser163Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs33927012 GRCh38 Chromosome 1, 17027802: 17027802
18 SDHB NM_003000.2(SDHB): c.418G> T (p.Val140Phe) single nucleotide variant Pathogenic/Likely pathogenic rs267607032 GRCh37 Chromosome 1, 17355100: 17355100
19 SDHB NM_003000.2(SDHB): c.418G> T (p.Val140Phe) single nucleotide variant Pathogenic/Likely pathogenic rs267607032 GRCh38 Chromosome 1, 17028605: 17028605
20 SDHB NC_000001.11: g.17048754_17064432del15679 deletion Pathogenic GRCh37 Chromosome 1, 17375249: 17390927
21 SDHB NC_000001.11: g.17048754_17064432del15679 deletion Pathogenic GRCh38 Chromosome 1, 17048754: 17064432
22 SDHB NC_000001.11: g.17050061_17070437del20377 deletion Pathogenic GRCh37 Chromosome 1, 17376556: 17396932
23 SDHB NC_000001.11: g.17050061_17070437del20377 deletion Pathogenic GRCh38 Chromosome 1, 17050061: 17070437
24 SDHB NM_003000.2(SDHB): c.423+1G> A single nucleotide variant Pathogenic rs398122805 GRCh37 Chromosome 1, 17355094: 17355094
25 SDHB NM_003000.2(SDHB): c.423+1G> A single nucleotide variant Pathogenic rs398122805 GRCh38 Chromosome 1, 17028599: 17028599
26 SDHB NM_003000.2(SDHB): c.32G> A (p.Arg11His) single nucleotide variant Conflicting interpretations of pathogenicity rs111430410 GRCh37 Chromosome 1, 17380483: 17380483
27 SDHB NM_003000.2(SDHB): c.32G> A (p.Arg11His) single nucleotide variant Conflicting interpretations of pathogenicity rs111430410 GRCh38 Chromosome 1, 17053988: 17053988
28 SDHB NM_003000.2(SDHB): c.423+20T> A single nucleotide variant Conflicting interpretations of pathogenicity rs190139590 GRCh37 Chromosome 1, 17355075: 17355075
29 SDHB NM_003000.2(SDHB): c.423+20T> A single nucleotide variant Conflicting interpretations of pathogenicity rs190139590 GRCh38 Chromosome 1, 17028580: 17028580
30 SDHB NM_003000.2(SDHB): c.143A> T (p.Asp48Val) single nucleotide variant Likely pathogenic rs202101384 GRCh37 Chromosome 1, 17371313: 17371313
31 SDHB NM_003000.2(SDHB): c.143A> T (p.Asp48Val) single nucleotide variant Likely pathogenic rs202101384 GRCh38 Chromosome 1, 17044818: 17044818
32 SDHB NM_003000.2(SDHB): c.403G> A (p.Val135Met) single nucleotide variant Uncertain significance rs201585157 GRCh37 Chromosome 1, 17355115: 17355115
33 SDHB NM_003000.2(SDHB): c.403G> A (p.Val135Met) single nucleotide variant Uncertain significance rs201585157 GRCh38 Chromosome 1, 17028620: 17028620
34 SDHB NM_003000.2(SDHB): c.638T> C (p.Met213Thr) single nucleotide variant Uncertain significance rs202014362 GRCh37 Chromosome 1, 17350472: 17350472
35 SDHB NM_003000.2(SDHB): c.638T> C (p.Met213Thr) single nucleotide variant Uncertain significance rs202014362 GRCh38 Chromosome 1, 17023977: 17023977
36 SDHB NM_003000.2(SDHB): c.287-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs397516833 GRCh37 Chromosome 1, 17355232: 17355232
37 SDHB NM_003000.2(SDHB): c.287-1G> C single nucleotide variant Pathogenic/Likely pathogenic rs397516833 GRCh38 Chromosome 1, 17028737: 17028737
38 SDHB NM_003000.2(SDHB): c.600G> A (p.Trp200Ter) single nucleotide variant Pathogenic/Likely pathogenic rs397516836 GRCh37 Chromosome 1, 17350510: 17350510
39 SDHB NM_003000.2(SDHB): c.600G> A (p.Trp200Ter) single nucleotide variant Pathogenic/Likely pathogenic rs397516836 GRCh38 Chromosome 1, 17024015: 17024015
40 SDHB NM_003000.2(SDHB): c.170A> G (p.His57Arg) single nucleotide variant Benign/Likely benign rs35962811 GRCh38 Chromosome 1, 17044791: 17044791
41 SDHB NM_003000.2(SDHB): c.170A> G (p.His57Arg) single nucleotide variant Benign/Likely benign rs35962811 GRCh37 Chromosome 1, 17371286: 17371286
42 SDHB NM_003000.2(SDHB): c.286+2T> A single nucleotide variant Pathogenic rs587781270 GRCh37 Chromosome 1, 17359553: 17359553
43 SDHB NM_003000.2(SDHB): c.286+2T> A single nucleotide variant Pathogenic rs587781270 GRCh38 Chromosome 1, 17033058: 17033058
44 SDHB NM_003000.2(SDHB): c.286G> A (p.Gly96Ser) single nucleotide variant Likely pathogenic rs587782243 GRCh37 Chromosome 1, 17359555: 17359555
45 SDHB NM_003000.2(SDHB): c.286G> A (p.Gly96Ser) single nucleotide variant Likely pathogenic rs587782243 GRCh38 Chromosome 1, 17033060: 17033060
46 SDHB NM_003000.2(SDHB): c.689G> A (p.Arg230His) single nucleotide variant Pathogenic rs587782604 GRCh37 Chromosome 1, 17349179: 17349179
47 SDHB NM_003000.2(SDHB): c.689G> A (p.Arg230His) single nucleotide variant Pathogenic rs587782604 GRCh38 Chromosome 1, 17022684: 17022684
48 SDHB NM_003000.2(SDHB): c.607_616delGGAGACAAAT (p.Gly203Ilefs) deletion Pathogenic rs587782617 GRCh37 Chromosome 1, 17350494: 17350503
49 SDHB NM_003000.2(SDHB): c.607_616delGGAGACAAAT (p.Gly203Ilefs) deletion Pathogenic rs587782617 GRCh38 Chromosome 1, 17023999: 17024008
50 SDHB NM_003000.2(SDHB): c.136C> T (p.Arg46Ter) single nucleotide variant Pathogenic rs74315370 GRCh37 Chromosome 1, 17371320: 17371320

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
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
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45 MeSH
46 MESH via Orphanet
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50 NCI
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58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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