HANAC
MCID: ANG060
MIFTS: 40

Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps (HANAC)

Categories: Blood diseases, Genetic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

MalaCards integrated aliases for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:

Name: Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps 58 30 6 41 74
Hanac Syndrome 54 26 60
Hanac 58 26 76
Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps Syndrome 54 26
Autosomal Dominant Familial Hematuria-Retinal Arteriolar Tortuosity-Contractures Syndrome 60
Autosomal Dominant Familial Hematuria, Retinal Arteriolar Tortuosity, Contractures 26
Hereditary Angiopathy with Nephropathy, Aneurysm, and Muscle Cramps Syndrome 26
Hereditary Angiopathy with Nephropathy, Aneurysms, and Muscle Cramps 38
Hereditary Angiopathy-Nephropathy-Aneurysms-Muscle Cramps Syndrome 60
Hereditary Angiopathy with Nephropathy Aneurysms and Muscle Cramps 76

Characteristics:

Orphanet epidemiological data:

60
hanac syndrome
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

58
Inheritance:
autosomal dominant


HPO:

33
angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 58 611773
KEGG 38 H00579
ICD10 via Orphanet 35 I99
UMLS via Orphanet 75 C2673195
Orphanet 60 ORPHA73229
MedGen 43 C2673195
UMLS 74 C2673195

Summaries for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

NIH Rare Diseases : 54 Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is a genetic condition that causes blood vessels to become fragile. Signs and symptoms include muscle cramps, Raynaud phenomenon, kidney cysts, blood in the urine (typically not visible to the eye), leukoencephalopathy (a change in brain tissue that can be seen on MRI), arteries in the back of the eye that twist and turn abnormally, headaches, and supraventricular arrhythmia. These signs and symptoms do not often cause serious complications, however temporary vision loss due to bleeding in the back of the eye, minor ischemic stroke, and bleeding complications with blood thinner use has been described. While muscle cramps may begin in childhood, many of the other symptoms do not appear until later in life. HANAC syndrome is caused by mutations in the COL4A1 gene. It is passed through families in a autosomal dominant fashion.

MalaCards based summary : Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps, also known as hanac syndrome, is related to porencephaly and kidney disease, and has symptoms including muscle cramp An important gene associated with Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps is COL4A1 (Collagen Type IV Alpha 1 Chain), and among its related pathways/superpathways are Focal adhesion and ECM-receptor interaction. Affiliated tissues include kidney, skin and brain, and related phenotypes are renal insufficiency and multiple renal cysts

Genetics Home Reference : 26 Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps (HANAC) syndrome is part of a group of conditions called the COL4A1-related disorders. The conditions in this group have a range of signs and symptoms that involve fragile blood vessels. HANAC syndrome is characterized by angiopathy, which is a disorder of the blood vessels. In people with HANAC syndrome, angiopathy affects several parts of the body. The blood vessels as well as thin sheet-like structures called basement membranes that separate and support cells are weakened and more susceptible to breakage.

UniProtKB/Swiss-Prot : 76 Hereditary angiopathy with nephropathy aneurysms and muscle cramps: The clinical renal manifestations include hematuria and bilateral large cysts. Histologic analysis revealed complex basement membrane defects in kidney and skin. The systemic angiopathy appears to affect both small vessels and large arteries.

Description from OMIM: 611773

Related Diseases for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Diseases related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 porencephaly 29.7 COL4A1 COL4A2
2 kidney disease 10.1
3 cerebrovascular disease 10.1
4 familial porencephaly 9.7 COL4A1 COL4A2
5 corneal dystrophy, posterior polymorphous, 3 9.7 COL4A1 COL4A2
6 hemorrhage, intracerebral 9.6 COL4A1 COL4A2
7 hemiplegia 9.5 COL4A1 COL4A2

Graphical network of the top 20 diseases related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:



Diseases related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps

Symptoms & Phenotypes for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Human phenotypes related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:

60 33 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 renal insufficiency 60 33 hallmark (90%) Very frequent (99-80%) HP:0000083
2 multiple renal cysts 60 33 hallmark (90%) Very frequent (99-80%) HP:0005562
3 retinal vascular tortuosity 60 33 hallmark (90%) Very frequent (99-80%) HP:0012841
4 muscle spasm 33 hallmark (90%) HP:0003394
5 hematuria 60 33 occasional (7.5%) Occasional (29-5%) HP:0000790
6 stroke 33 occasional (7.5%) HP:0001297
7 nephropathy 33 HP:0000112
8 supraventricular arrhythmia 33 HP:0005115
9 muscle cramps 60 Very frequent (99-80%)
10 retinal arteriolar tortuosity 33 HP:0001136
11 retinal hemorrhage 33 HP:0000573
12 renal cyst 33 HP:0000107
13 raynaud phenomenon 33 HP:0030880
14 dilatation of the cerebral artery 33 HP:0004944
15 leukoencephalopathy 33 HP:0002352

Symptoms via clinical synopsis from OMIM:

58
Muscle Soft Tissue:
muscle cramps

Cardiovascular Vascular:
raynaud phenomenon
aneurysms of right internal carotid artery, intracranial segment
aneurysm of right middle cerebral artery, horizontal segment

Cardiovascular Heart:
arrhythmias, supraventricular

Skin Nails Hair Nails:
capillary tortuosity in nail beds

Laboratory Abnormalities:
creatine kinase, serum, elevated
glomerular filtration rate, decreased

Head And Neck Eyes:
retinal arteriolar tortuosity
retinal hemorrhage

Genitourinary Kidneys:
renal cysts
hematuria, microscopic
hematuria, gross (in some patients)
renal failure, mild
basement membrane alterations in bowman capsule, tubules, and interstitial capillaries, with irregular thickening, splitting into multiple layers, and electron-lucent areas
more
Skin Nails Hair Skin Electron Microscopy:
basement membrane duplications at dermoepidermal junction
dermal arteriole dissociation in vascular smooth muscle cells
basement membrane abnormally spread in vascular smooth muscle cells

Neurologic Central Nervous System:
leukoencephalopathy, periventricular
microvascular spaces, dilated
cerebrovascular accident (in some patients)

Clinical features from OMIM:

611773

UMLS symptoms related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:


muscle cramp

Drugs & Therapeutics for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Search Clinical Trials , NIH Clinical Center for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps

Genetic Tests for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Genetic tests related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:

# Genetic test Affiliating Genes
1 Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps 30 COL4A1

Anatomical Context for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

MalaCards organs/tissues related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:

42
Kidney, Skin, Brain, Eye, Smooth Muscle

Publications for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Articles related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:

# Title Authors Year
1
An unusual phenocopy of the HANAC syndrome without genetic involvement of COL4A1/COL4A2. ( 29423873 )
2018
2
Col4a1 mutation generates vascular abnormalities correlated with neuronal damage in a mouse model of HANAC syndrome. ( 28057519 )
2017
3
HANAC Syndrome Col4a1 Mutation Causes Neonate Glomerular Hyperpermeability and Adult Glomerulocystic Kidney Disease. ( 26260163 )
2016
4
Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain. ( 20818663 )
2010
5
Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. ( 19949034 )
2009

Variations for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

UniProtKB/Swiss-Prot genetic disease variations for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:

76
# Symbol AA change Variation ID SNP ID
1 COL4A1 p.Gly498Val VAR_044159 rs113994104
2 COL4A1 p.Gly519Arg VAR_044160 rs113994105
3 COL4A1 p.Gly528Glu VAR_044161 rs113994106
4 COL4A1 p.Gly498Arg VAR_064493 rs267606744
5 COL4A1 p.Gly510Arg VAR_064494 rs267606743
6 COL4A1 p.Gly525Leu VAR_064495

ClinVar genetic disease variations for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps:

6 (show top 50) (show all 258)
# Gene Variation Type Significance SNP ID Assembly Location
1 COL4A1; COL4A2 NM_001845.5(COL4A1): c.19G> C (p.Val7Leu) single nucleotide variant Benign rs9515185 GRCh37 Chromosome 13, 110959356: 110959356
2 COL4A1; COL4A2 NM_001845.5(COL4A1): c.19G> C (p.Val7Leu) single nucleotide variant Benign rs9515185 GRCh38 Chromosome 13, 110307009: 110307009
3 COL4A1 NM_001845.5(COL4A1): c.1466-6C> T single nucleotide variant Conflicting interpretations of pathogenicity rs183563055 GRCh37 Chromosome 13, 110844637: 110844637
4 COL4A1 NM_001845.5(COL4A1): c.1466-6C> T single nucleotide variant Conflicting interpretations of pathogenicity rs183563055 GRCh38 Chromosome 13, 110192290: 110192290
5 COL4A1 NM_001845.5(COL4A1): c.1588C> T (p.Pro530Ser) single nucleotide variant Uncertain significance rs145172612 GRCh37 Chromosome 13, 110839625: 110839625
6 COL4A1 NM_001845.5(COL4A1): c.1588C> T (p.Pro530Ser) single nucleotide variant Uncertain significance rs145172612 GRCh38 Chromosome 13, 110187278: 110187278
7 COL4A1 NM_001845.5(COL4A1): c.1815T> C (p.Pro605=) single nucleotide variant Benign rs61749897 GRCh37 Chromosome 13, 110838814: 110838814
8 COL4A1 NM_001845.5(COL4A1): c.1815T> C (p.Pro605=) single nucleotide variant Benign rs61749897 GRCh38 Chromosome 13, 110186467: 110186467
9 COL4A1 NM_001845.5(COL4A1): c.161C> T (p.Pro54Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs34004222 GRCh37 Chromosome 13, 110866346: 110866346
10 COL4A1 NM_001845.5(COL4A1): c.161C> T (p.Pro54Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs34004222 GRCh38 Chromosome 13, 110213999: 110213999
11 COL4A1 NM_001845.5(COL4A1): c.234+8C> T single nucleotide variant Benign rs9521650 GRCh37 Chromosome 13, 110866265: 110866265
12 COL4A1 NM_001845.5(COL4A1): c.234+8C> T single nucleotide variant Benign rs9521650 GRCh38 Chromosome 13, 110213918: 110213918
13 COL4A1 NM_001845.5(COL4A1): c.3996C> T (p.Gly1332=) single nucleotide variant Benign rs150857429 GRCh37 Chromosome 13, 110818604: 110818604
14 COL4A1 NM_001845.5(COL4A1): c.3996C> T (p.Gly1332=) single nucleotide variant Benign rs150857429 GRCh38 Chromosome 13, 110166257: 110166257
15 COL4A1 NM_001845.5(COL4A1): c.4002A> C (p.Gln1334His) single nucleotide variant Benign rs3742207 GRCh37 Chromosome 13, 110818598: 110818598
16 COL4A1 NM_001845.5(COL4A1): c.4002A> C (p.Gln1334His) single nucleotide variant Benign rs3742207 GRCh38 Chromosome 13, 110166251: 110166251
17 COL4A1 NM_001845.5(COL4A1): c.4056C> T (p.Tyr1352=) single nucleotide variant Likely benign rs140210015 GRCh37 Chromosome 13, 110817303: 110817303
18 COL4A1 NM_001845.5(COL4A1): c.4056C> T (p.Tyr1352=) single nucleotide variant Likely benign rs140210015 GRCh38 Chromosome 13, 110164956: 110164956
19 COL4A1 NM_001845.5(COL4A1): c.393G> A (p.Glu131=) single nucleotide variant Benign/Likely benign rs34458255 GRCh37 Chromosome 13, 110864264: 110864264
20 COL4A1 NM_001845.5(COL4A1): c.393G> A (p.Glu131=) single nucleotide variant Benign/Likely benign rs34458255 GRCh38 Chromosome 13, 110211917: 110211917
21 COL4A1 NM_001845.5(COL4A1): c.1493G> T (p.Gly498Val) single nucleotide variant Pathogenic rs113994104 GRCh37 Chromosome 13, 110844604: 110844604
22 COL4A1 NM_001845.5(COL4A1): c.1493G> T (p.Gly498Val) single nucleotide variant Pathogenic rs113994104 GRCh38 Chromosome 13, 110192257: 110192257
23 COL4A1 NM_001845.5(COL4A1): c.1555G> A (p.Gly519Arg) single nucleotide variant Pathogenic rs113994105 GRCh37 Chromosome 13, 110839658: 110839658
24 COL4A1 NM_001845.5(COL4A1): c.1555G> A (p.Gly519Arg) single nucleotide variant Pathogenic rs113994105 GRCh38 Chromosome 13, 110187311: 110187311
25 COL4A1 NM_001845.5(COL4A1): c.1583G> A (p.Gly528Glu) single nucleotide variant Pathogenic rs113994106 GRCh37 Chromosome 13, 110839630: 110839630
26 COL4A1 NM_001845.5(COL4A1): c.1583G> A (p.Gly528Glu) single nucleotide variant Pathogenic rs113994106 GRCh38 Chromosome 13, 110187283: 110187283
27 COL4A1 NM_001845.5(COL4A1): c.1492G> C (p.Gly498Arg) single nucleotide variant Pathogenic rs267606744 GRCh37 Chromosome 13, 110844605: 110844605
28 COL4A1 NM_001845.5(COL4A1): c.1492G> C (p.Gly498Arg) single nucleotide variant Pathogenic rs267606744 GRCh38 Chromosome 13, 110192258: 110192258
29 COL4A1 NM_001845.5(COL4A1): c.1528G> A (p.Gly510Arg) single nucleotide variant Pathogenic rs267606743 GRCh37 Chromosome 13, 110844569: 110844569
30 COL4A1 NM_001845.5(COL4A1): c.1528G> A (p.Gly510Arg) single nucleotide variant Pathogenic rs267606743 GRCh38 Chromosome 13, 110192222: 110192222
31 COL4A1 NM_001845.5(COL4A1): c.1573_1574delGGinsTT (p.Gly525Leu) indel Pathogenic rs281865426 GRCh37 Chromosome 13, 110839639: 110839640
32 COL4A1 NM_001845.5(COL4A1): c.1573_1574delGGinsTT (p.Gly525Leu) indel Pathogenic rs281865426 GRCh38 Chromosome 13, 110187292: 110187293
33 COL4A1 NM_001845.5(COL4A1): c.4800C> T (p.Ser1600=) single nucleotide variant Benign rs650724 GRCh38 Chromosome 13, 110152462: 110152462
34 COL4A1 NM_001845.5(COL4A1): c.4800C> T (p.Ser1600=) single nucleotide variant Benign rs650724 GRCh37 Chromosome 13, 110804809: 110804809
35 COL4A1 NM_001845.5(COL4A1): c.4797G> A (p.Ala1599=) single nucleotide variant Likely benign rs146638269 GRCh37 Chromosome 13, 110804812: 110804812
36 COL4A1 NM_001845.5(COL4A1): c.4797G> A (p.Ala1599=) single nucleotide variant Likely benign rs146638269 GRCh38 Chromosome 13, 110152465: 110152465
37 COL4A1 NM_001845.5(COL4A1): c.4640+7C> T single nucleotide variant Benign rs2275843 GRCh38 Chromosome 13, 110161185: 110161185
38 COL4A1 NM_001845.5(COL4A1): c.4640+7C> T single nucleotide variant Benign rs2275843 GRCh37 Chromosome 13, 110813532: 110813532
39 COL4A1 NM_001845.5(COL4A1): c.4470C> T (p.Ala1490=) single nucleotide variant Benign rs1133219 GRCh38 Chromosome 13, 110161362: 110161362
40 COL4A1 NM_001845.5(COL4A1): c.4470C> T (p.Ala1490=) single nucleotide variant Benign rs1133219 GRCh37 Chromosome 13, 110813709: 110813709
41 COL4A1 NM_001845.5(COL4A1): c.3877-9C> T single nucleotide variant Benign rs589985 GRCh37 Chromosome 13, 110819586: 110819586
42 COL4A1 NM_001845.5(COL4A1): c.3877-9C> T single nucleotide variant Benign rs589985 GRCh38 Chromosome 13, 110167239: 110167239
43 COL4A1 NM_001845.5(COL4A1): c.3693G> A (p.Thr1231=) single nucleotide variant Benign rs117738194 GRCh37 Chromosome 13, 110822943: 110822943
44 COL4A1 NM_001845.5(COL4A1): c.3693G> A (p.Thr1231=) single nucleotide variant Benign rs117738194 GRCh38 Chromosome 13, 110170596: 110170596
45 COL4A1 NM_001845.5(COL4A1): c.3189A> T (p.Arg1063=) single nucleotide variant Benign rs874203 GRCh37 Chromosome 13, 110827574: 110827574
46 COL4A1 NM_001845.5(COL4A1): c.3189A> T (p.Arg1063=) single nucleotide variant Benign rs874203 GRCh38 Chromosome 13, 110175227: 110175227
47 COL4A1 NM_001845.5(COL4A1): c.3183G> A (p.Gly1061=) single nucleotide variant Benign rs874204 GRCh38 Chromosome 13, 110175233: 110175233
48 COL4A1 NM_001845.5(COL4A1): c.3183G> A (p.Gly1061=) single nucleotide variant Benign rs874204 GRCh37 Chromosome 13, 110827580: 110827580
49 COL4A1 NM_001845.5(COL4A1): c.2130G> A (p.Pro710=) single nucleotide variant Benign rs16975492 GRCh38 Chromosome 13, 110181355: 110181355
50 COL4A1 NM_001845.5(COL4A1): c.2130G> A (p.Pro710=) single nucleotide variant Benign rs16975492 GRCh37 Chromosome 13, 110833702: 110833702

Expression for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Search GEO for disease gene expression data for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps.

Pathways for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Pathways related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps according to KEGG:

38
# Name Kegg Source Accession
1 Focal adhesion hsa04510
2 ECM-receptor interaction hsa04512

Pathways related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps according to GeneCards Suite gene sharing:

(show all 19)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.42 COL4A1 COL4A2
2
Show member pathways
12.34 COL4A1 COL4A2
3 12.27 COL4A1 COL4A2
4
Show member pathways
12.26 COL4A1 COL4A2
5
Show member pathways
12.18 COL4A1 COL4A2
6
Show member pathways
12.07 COL4A1 COL4A2
7
Show member pathways
11.67 COL4A1 COL4A2
8
Show member pathways
11.67 COL4A1 COL4A2
9
Show member pathways
11.49 COL4A1 COL4A2
10 11.46 COL4A1 COL4A2
11 11.42 COL4A1 COL4A2
12 11.37 COL4A1 COL4A2
13 11.15 COL4A1 COL4A2
14 11.03 COL4A1 COL4A2
15 10.95 COL4A1 COL4A2
16 10.79 COL4A1 COL4A2
17 10.56 COL4A1 COL4A2
18 10.46 COL4A1 COL4A2
19 10.19 COL4A1 COL4A2

GO Terms for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

Cellular components related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix GO:0031012 9.37 COL4A1 COL4A2
2 endoplasmic reticulum lumen GO:0005788 9.32 COL4A1 COL4A2
3 collagen-containing extracellular matrix GO:0062023 9.26 COL4A1 COL4A2
4 basement membrane GO:0005604 9.16 COL4A1 COL4A2
5 collagen trimer GO:0005581 8.96 COL4A1 COL4A2
6 collagen type IV trimer GO:0005587 8.62 COL4A1 COL4A2

Biological processes related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix organization GO:0030198 8.96 COL4A1 COL4A2
2 collagen-activated tyrosine kinase receptor signaling pathway GO:0038063 8.62 COL4A1 COL4A2

Molecular functions related to Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular matrix structural constituent GO:0005201 8.96 COL4A1 COL4A2
2 extracellular matrix structural constituent conferring tensile strength GO:0030020 8.62 COL4A1 COL4A2

Sources for Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle...

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10 dbSNP
11 DGIdb
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20 FMA
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35 ICD10 via Orphanet
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59 OMIM via Orphanet
63 PubMed
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70 SNOMED-CT via HPO
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75 UMLS via Orphanet
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