GACI2
MCID: ART102
MIFTS: 25

Arterial Calcification, Generalized, of Infancy, 2 (GACI2)

Categories: Cardiovascular diseases, Genetic diseases, Muscle diseases

Aliases & Classifications for Arterial Calcification, Generalized, of Infancy, 2

MalaCards integrated aliases for Arterial Calcification, Generalized, of Infancy, 2:

Name: Arterial Calcification, Generalized, of Infancy, 2 57 13 70
Generalized Arterial Calcification of Infancy 2 29 6
Gaci2 57 72
Calcification, Arterial, Generalized, of Infancy, Type 2 39
Arterial Calcification of Infancy, Generalized, 2 72

Characteristics:

OMIM®:

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

Miscellaneous:
most patients die in infancy features of pseudoxanthoma elasticum, an allelic disorder, have not yet been reported in gaci2 patients (the 4 surviving patients reported as of january 2012 are all age 5 years or less)


HPO:

31
arterial calcification, generalized, of infancy, 2:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM® 57 614473
OMIM Phenotypic Series 57 PS208000
MeSH 44 D061205
UMLS 70 C3276161

Summaries for Arterial Calcification, Generalized, of Infancy, 2

OMIM® : 57 Generalized arterial calcification of infancy (GACI) is a severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. GACI is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure (summary by Rutsch et al., 2003 and Cheng et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of GACI, see GACI1 (208000). Pseudoxanthoma elasticum (PXE; 264800) is an allelic disorder caused by mutation in the ABCC6 gene; it has been suggested that GACI and PXE represent 2 ends of a clinical spectrum of ectopic calcification and other organ pathologies rather than 2 distinct disorders (Nitschke et al., 2012). (614473) (Updated 05-Apr-2021)

MalaCards based summary : Arterial Calcification, Generalized, of Infancy, 2, also known as generalized arterial calcification of infancy 2, is related to pseudoxanthoma elasticum. An important gene associated with Arterial Calcification, Generalized, of Infancy, 2 is ABCC6 (ATP Binding Cassette Subfamily C Member 6). Affiliated tissues include heart, and related phenotypes are hypertension and myocardial infarction

UniProtKB/Swiss-Prot : 72 Arterial calcification of infancy, generalized, 2: A severe autosomal recessive disorder characterized by calcification of the internal elastic lamina of muscular arteries and stenosis due to myointimal proliferation. The disorder is often fatal within the first 6 months of life because of myocardial ischemia resulting in refractory heart failure.

Related Diseases for Arterial Calcification, Generalized, of Infancy, 2

Diseases in the Arterial Calcification, Generalized, of Infancy, 1 family:

Arterial Calcification, Generalized, of Infancy, 2

Diseases related to Arterial Calcification, Generalized, of Infancy, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pseudoxanthoma elasticum 11.0

Symptoms & Phenotypes for Arterial Calcification, Generalized, of Infancy, 2

Human phenotypes related to Arterial Calcification, Generalized, of Infancy, 2:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 hypertension 31 occasional (7.5%) HP:0000822
2 myocardial infarction 31 occasional (7.5%) HP:0001658
3 nephrocalcinosis 31 occasional (7.5%) HP:0000121
4 hypophosphatemic rickets 31 occasional (7.5%) HP:0004912
5 congestive heart failure 31 HP:0001635
6 coronary artery calcification 31 HP:0001717

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Cardiovascular Heart:
coronary artery calcification
heart failure
cardiac dysfunction
myocardial infarction (in some patients)

Skeletal Limbs:
hypophosphatemic rickets (in some patients)

Genitourinary Kidneys:
nephrocalcinosis (in some patients)
calcification of renal arteries
tubular calcification (in some patients)

Cardiovascular Vascular:
hypertension (in some patients)
generalized calcification of arteries, including aorta and intraparenchymal arteries

Metabolic Features:
hypophosphatemic rickets (in some patients)

Clinical features from OMIM®:

614473 (Updated 05-Apr-2021)

Drugs & Therapeutics for Arterial Calcification, Generalized, of Infancy, 2

Search Clinical Trials , NIH Clinical Center for Arterial Calcification, Generalized, of Infancy, 2

Genetic Tests for Arterial Calcification, Generalized, of Infancy, 2

Genetic tests related to Arterial Calcification, Generalized, of Infancy, 2:

# Genetic test Affiliating Genes
1 Generalized Arterial Calcification of Infancy 2 29 ABCC6

Anatomical Context for Arterial Calcification, Generalized, of Infancy, 2

MalaCards organs/tissues related to Arterial Calcification, Generalized, of Infancy, 2:

40
Heart

Publications for Arterial Calcification, Generalized, of Infancy, 2

Articles related to Arterial Calcification, Generalized, of Infancy, 2:

(show all 15)
# Title Authors PMID Year
1
Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6. 57 6
22209248 2012
2
An unusual severe vascular case of pseudoxanthoma elasticum presenting as generalized arterial calcification of infancy. 6 57
20034067 2010
3
Idiopathic infantile arterial calcification: two case reports, a review of the literature and a role for cardiac transplantation. 57 6
16573612 2006
4
Mutation spectrum in the ABCC6 gene and genotype-phenotype correlations in a French cohort with pseudoxanthoma elasticum. 6
28102862 2017
5
Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes. 6
18800149 2009
6
Pseudoxanthoma elasticum: the end of the autosomal dominant segregation myth. 6
16541094 2006
7
Molecular genetics of pseudoxanthoma elasticum: type and frequency of mutations in ABCC6. 6
16086317 2005
8
Generalized arterial calcification of infancy: different clinical courses in two affected siblings. 57
15940697 2005
9
Mutations in ENPP1 are associated with 'idiopathic' infantile arterial calcification. 57
12881724 2003
10
Analysis of the frequent R1141X mutation in the ABCC6 gene in pseudoxanthoma elasticum. 6
12714611 2003
11
Evidence for a founder effect for pseudoxanthoma elasticum in the Afrikaner population of South Africa. 6
12384774 2002
12
Frequent mutation in the ABCC6 gene (R1141X) is associated with a strong increase in the prevalence of coronary artery disease. 6
12176944 2002
13
Compound heterozygosity for a recurrent 16.5-kb Alu-mediated deletion mutation and single-base-pair substitutions in the ABCC6 gene results in pseudoxanthoma elasticum. 6
11179012 2001
14
Pseudoxanthoma elasticum: Point mutations in the ABCC6 gene and a large deletion including also ABCC1 and MYH11. 6
11439001 2001
15
Pseudoxanthoma elasticum: mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter. 6
10811882 2000

Variations for Arterial Calcification, Generalized, of Infancy, 2

ClinVar genetic disease variations for Arterial Calcification, Generalized, of Infancy, 2:

6 (show all 27)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ABCC6 NM_001171.5(ABCC6):c.1552C>T (p.Arg518Ter) SNV Pathogenic 30339 rs72650700 GRCh37: 16:16284104-16284104
GRCh38: 16:16190247-16190247
2 ABCC6 NM_001171.5(ABCC6):c.3940C>T (p.Arg1314Trp) SNV Pathogenic 6564 rs63750759 GRCh37: 16:16248831-16248831
GRCh38: 16:16154974-16154974
3 ABCC6 NM_001171.5(ABCC6):c.2294G>A (p.Arg765Gln) SNV Pathogenic 30337 rs67561842 GRCh37: 16:16272776-16272776
GRCh38: 16:16178919-16178919
4 ABCC6 NM_001171.5(ABCC6):c.4216C>A (p.Gln1406Lys) SNV Pathogenic 30338 rs387906859 GRCh37: 16:16244622-16244622
GRCh38: 16:16150765-16150765
5 ABCC6 NM_001171.5(ABCC6):c.2787+1G>T SNV Pathogenic 6560 rs72664209 GRCh37: 16:16267140-16267140
GRCh38: 16:16173283-16173283
6 ABCC6 NM_001171.5(ABCC6):c.3904G>A (p.Gly1302Arg) SNV Pathogenic 6579 rs63749856 GRCh37: 16:16248867-16248867
GRCh38: 16:16155010-16155010
7 ABCC6 NM_001171.5(ABCC6):c.3412C>T (p.Arg1138Trp) SNV Pathogenic 6571 rs28939701 GRCh37: 16:16256944-16256944
GRCh38: 16:16163087-16163087
8 ABCC6 NM_001171.5(ABCC6):c.2787+1G>T SNV Pathogenic 6560 rs72664209 GRCh37: 16:16267140-16267140
GRCh38: 16:16173283-16173283
9 ABCC6 NM_001171.5(ABCC6):c.1553G>A (p.Arg518Gln) SNV Pathogenic 265018 rs72653772 GRCh37: 16:16284103-16284103
GRCh38: 16:16190246-16190246
10 ABCC6 GRCh37/hg19 16p13.11(chr16:16248791-16260443) copy number loss Pathogenic 870399 GRCh37: 16:16248791-16260443
GRCh38:
11 ABCC6 NM_001171.5(ABCC6):c.1999del (p.Ala667fs) Deletion Pathogenic 433256 rs72664227 GRCh37: 16:16276732-16276732
GRCh38: 16:16182875-16182875
12 ABCC6 NM_001171.6(ABCC6):c.615_616dup (p.Thr206fs) Microsatellite Pathogenic 998293 GRCh37: 16:16306087-16306088
GRCh38: 16:16212230-16212231
13 ABCC6 NM_001171.5(ABCC6):c.3736-1G>A SNV Pathogenic 6574 rs63750273 GRCh37: 16:16251667-16251667
GRCh38: 16:16157810-16157810
14 ABCC6 NM_001171.5(ABCC6):c.3421C>T (p.Arg1141Ter) SNV Pathogenic 6559 rs72653706 GRCh37: 16:16256935-16256935
GRCh38: 16:16163078-16163078
15 ABCC6 NM_001171.5(ABCC6):c.450dup (p.Ala151fs) Duplication Pathogenic 30340 rs387906860 GRCh37: 16:16313434-16313435
GRCh38: 16:16219577-16219578
16 ABCC6 NM_001171.5(ABCC6):c.3421C>T (p.Arg1141Ter) SNV Pathogenic 6559 rs72653706 GRCh37: 16:16256935-16256935
GRCh38: 16:16163078-16163078
17 ABCC6 NM_001171.6(ABCC6):c.2071-1G>A SNV Pathogenic 1033352 GRCh37: 16:16276446-16276446
GRCh38: 16:16182589-16182589
18 ABCC6 NM_001171.5(ABCC6):c.3490C>T (p.Arg1164Ter) SNV Pathogenic 6572 rs72653744 GRCh37: 16:16256866-16256866
GRCh38: 16:16163009-16163009
19 ABCC6 NM_001171.6(ABCC6):c.3900del (p.Thr1301fs) Deletion Pathogenic 1033354 GRCh37: 16:16248871-16248871
GRCh38: 16:16155014-16155014
20 ABCC6 NM_001171.6(ABCC6):c.3892G>A (p.Val1298Ile) SNV Likely pathogenic 930520 GRCh37: 16:16248879-16248879
GRCh38: 16:16155022-16155022
21 ABCC6 NM_001171.6(ABCC6):c.2836del (p.Leu946fs) Deletion Likely pathogenic 930527 GRCh37: 16:16263662-16263662
GRCh38: 16:16169805-16169805
22 ABCC6 NM_001171.5(ABCC6):c.2097G>T (p.Glu699Asp) SNV Likely pathogenic 433259 rs72653784 GRCh37: 16:16276419-16276419
GRCh38: 16:16182562-16182562
23 ABCC6 NM_001171.5(ABCC6):c.1108A>G (p.Asn370Asp) SNV Uncertain significance 433220 rs72653760 GRCh37: 16:16295926-16295926
GRCh38: 16:16202069-16202069
24 ABCC6 NM_001171.6(ABCC6):c.1214C>T (p.Ala405Val) SNV Uncertain significance 1030271 GRCh37: 16:16292002-16292002
GRCh38: 16:16198145-16198145
25 ABCC6 NM_001171.5(ABCC6):c.1424A>T (p.His475Leu) SNV Uncertain significance 291095 rs151187637 GRCh37: 16:16286694-16286694
GRCh38: 16:16192837-16192837
26 ABCC6 NM_001171.6(ABCC6):c.3952G>A (p.Ala1318Thr) SNV Uncertain significance 1033355 GRCh37: 16:16248819-16248819
GRCh38: 16:16154962-16154962
27 ABCC6 NM_001171.6(ABCC6):c.469G>A (p.Gly157Arg) SNV Uncertain significance 1033356 GRCh37: 16:16313416-16313416
GRCh38: 16:16219559-16219559

UniProtKB/Swiss-Prot genetic disease variations for Arterial Calcification, Generalized, of Infancy, 2:

72
# Symbol AA change Variation ID SNP ID
1 ABCC6 p.Arg1314Trp VAR_011495 rs63750759
2 ABCC6 p.Leu355Arg VAR_067846 rs72653758
3 ABCC6 p.Arg391Gly VAR_067850 rs72653762
4 ABCC6 p.Ser590Phe VAR_067860 rs537233133
5 ABCC6 p.Arg1114Cys VAR_067890 rs63749794
6 ABCC6 p.Arg1221His VAR_067897 rs63751001

Expression for Arterial Calcification, Generalized, of Infancy, 2

Search GEO for disease gene expression data for Arterial Calcification, Generalized, of Infancy, 2.

Pathways for Arterial Calcification, Generalized, of Infancy, 2

GO Terms for Arterial Calcification, Generalized, of Infancy, 2

Sources for Arterial Calcification, Generalized, of Infancy, 2

3 CDC
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11 DGIdb
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56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
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71 UMLS via Orphanet
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