ACG1B
MCID: ACH042
MIFTS: 45

Achondrogenesis, Type Ib (ACG1B)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Achondrogenesis, Type Ib

MalaCards integrated aliases for Achondrogenesis, Type Ib:

Name: Achondrogenesis, Type Ib 57 29 55 6 40 73
Achondrogenesis Type Ib 12 75 37 15
Achondrogenesis Type 1b 76 24 53 59
Acg1b 57 24 53 75
Achondrogenesis Fraccaro Type 12 53 75
Fraccaro Achondrogenesis 53 75
Achondrogenesis Ib 57 13
Achondrogenesis, Parenti-Fraccaro Type 59
Achondrogenesis, Fraccaro Type 57
Achondrogenesis 1b 75
Acg-Ib 75

Characteristics:

Orphanet epidemiological data:

59
achondrogenesis type 1b
Inheritance: Autosomal recessive; Age of onset: Antenatal,Neonatal; Age of death: infantile,stillbirth;

OMIM:

57
Inheritance:
autosomal recessive


HPO:

32
achondrogenesis, type ib:
Mortality/Aging stillbirth
Inheritance autosomal recessive inheritance


GeneReviews:

24
Penetrance For pathogenic variants in slc26a2, penetrance is complete...

Classifications:



Summaries for Achondrogenesis, Type Ib

OMIM : 57 The term achondrogenesis has been used to characterize the most severe forms of chondrodysplasia in humans, invariably lethal before or shortly after birth. Achondrogenesis type I is a severe chondrodystrophy characterized radiographically by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death (Maroteaux and Lamy, 1968; Langer et al., 1969). In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. (600972)

MalaCards based summary : Achondrogenesis, Type Ib, also known as achondrogenesis type ib, is related to diastrophic dysplasia and achondrogenesis, type ii. An important gene associated with Achondrogenesis, Type Ib is SLC26A2 (Solute Carrier Family 26 Member 2), and among its related pathways/superpathways are ECM proteoglycans and Articular Cartilage Extracellular Matrix Pathway. Affiliated tissues include bone, lung and skin, and related phenotypes are macrocephaly and short neck

Disease Ontology : 12 An achondrogenesis that has material basis in mutation in the SLC26A2 gene which results in umbilical or inguinal hernia and a prominent rounded abdomen.

UniProtKB/Swiss-Prot : 75 Achondrogenesis 1B: A form of achondrogenesis type 1, a lethal form of chondrodysplasia characterized by deficient ossification in the lumbar vertebrae and absent ossification in the sacral, pubic and ischial bones and clinically by stillbirth or early death. In addition to severe micromelia, there is a disproportionately large cranium due to marked edema of soft tissues. ACG1B is an autosomal recessive disease.

Wikipedia : 76 Achondrogenesis, type 1B is a severe autosomal recessive skeletal disorder, invariably fatal in the... more...

GeneReviews: NBK1516

Related Diseases for Achondrogenesis, Type Ib

Graphical network of the top 20 diseases related to Achondrogenesis, Type Ib:



Diseases related to Achondrogenesis, Type Ib

Symptoms & Phenotypes for Achondrogenesis, Type Ib

Symptoms via clinical synopsis from OMIM:

57
Respiratory Lung:
respiratory insufficiency

Chest External Features:
narrow chest

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Skeletal Pelvis:
small iliac bones
unossified ischium and pubis

Skeletal Limbs:
severe micromelia
marked shortness, broad tubular bone
metaphyseal spurring

Chest Ribs Sternum Clavicles And Scapulae:
thin short ribs
occasional rib fractures

Prenatal Manifestations Delivery:
breech presentation at birth
often stillborn

Abdomen External Features:
umbilical hernia
distended abdomen
inguinal herniae

Head And Neck Head:
flat face

Skeletal Spine:
absent or minimally ossified vertebral bodies

Growth Other:
fetal hydrops

Growth Height:
short-limbed dwarfism identifiable at birth

Skeletal Skull:
slightly less ossified than expected for gestational age

Laboratory Abnormalities:
no cartilage staining with toluidine blue
impaired synthesis of fibroblast sulfated proteoglycans


Clinical features from OMIM:

600972

Human phenotypes related to Achondrogenesis, Type Ib:

59 32 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000256
2 short neck 59 32 hallmark (90%) Very frequent (99-80%) HP:0000470
3 frontal bossing 59 32 hallmark (90%) Very frequent (99-80%) HP:0002007
4 umbilical hernia 59 32 frequent (33%) Frequent (79-30%) HP:0001537
5 short nose 59 32 hallmark (90%) Very frequent (99-80%) HP:0003196
6 anteverted nares 59 32 hallmark (90%) Very frequent (99-80%) HP:0000463
7 long philtrum 59 32 hallmark (90%) Very frequent (99-80%) HP:0000343
8 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
9 narrow chest 59 32 hallmark (90%) Very frequent (99-80%) HP:0000774
10 micromelia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002983
11 short foot 59 32 hallmark (90%) Very frequent (99-80%) HP:0001773
12 short thorax 59 32 hallmark (90%) Very frequent (99-80%) HP:0010306
13 hydrops fetalis 59 32 hallmark (90%) Very frequent (99-80%) HP:0001789
14 flat face 59 32 hallmark (90%) Very frequent (99-80%) HP:0012368
15 thickened nuchal skin fold 59 32 hallmark (90%) Very frequent (99-80%) HP:0000474
16 cystic hygroma 59 32 occasional (7.5%) Occasional (29-5%) HP:0000476
17 talipes equinovarus 59 32 frequent (33%) Frequent (79-30%) HP:0001762
18 polyhydramnios 59 32 frequent (33%) Frequent (79-30%) HP:0001561
19 abnormality of the ribs 59 32 frequent (33%) Frequent (79-30%) HP:0000772
20 severe short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0003510
21 aplasia/hypoplasia of the lungs 59 32 hallmark (90%) Very frequent (99-80%) HP:0006703
22 disproportionate short stature 59 32 hallmark (90%) Very frequent (99-80%) HP:0003498
23 abnormal enchondral ossification 59 32 hallmark (90%) Very frequent (99-80%) HP:0003336
24 lethal skeletal dysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0005716
25 femoral hernia 59 32 frequent (33%) Frequent (79-30%) HP:0100541
26 malar flattening 32 HP:0000272
27 respiratory insufficiency 32 HP:0002093
28 inguinal hernia 32 HP:0000023
29 edema 32 HP:0000969
30 malformation of the heart and great vessels 59 Occasional (29-5%)
31 neonatal short-limb short stature 32 HP:0008921
32 abdominal distention 32 HP:0003270
33 breech presentation 32 HP:0001623
34 abnormality of cardiovascular system morphology 32 occasional (7.5%) HP:0030680
35 hypoplastic ilia 32 HP:0000946
36 short ribs 32 HP:0000773
37 absent or minimally ossified vertebral bodies 32 HP:0004599

MGI Mouse Phenotypes related to Achondrogenesis, Type Ib:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 9.46 BGN DCN FLNB SLC26A2
2 growth/size/body region MP:0005378 9.43 BGN DCN FLNB SLC26A2 SLC26A3 SLC26A5
3 skeleton MP:0005390 9.02 BGN DCN FLNB SLC26A2 SLC26A4

Drugs & Therapeutics for Achondrogenesis, Type Ib

Search Clinical Trials , NIH Clinical Center for Achondrogenesis, Type Ib

Genetic Tests for Achondrogenesis, Type Ib

Genetic tests related to Achondrogenesis, Type Ib:

# Genetic test Affiliating Genes
1 Achondrogenesis, Type Ib 29 SLC26A2

Anatomical Context for Achondrogenesis, Type Ib

MalaCards organs/tissues related to Achondrogenesis, Type Ib:

41
Bone, Lung, Skin, Heart

Publications for Achondrogenesis, Type Ib

Articles related to Achondrogenesis, Type Ib:

# Title Authors Year
1
Achondrogenesis type IB: agenesis of cartilage interterritorial matrix as the link between gene defect and pathological skeletal phenotype. ( 11570921 )
2001
2
Achondrogenesis type IB is caused by mutations in the diastrophic dysplasia sulphate transporter gene. ( 8528239 )
1996
3
Achondrogenesis type IB (Fraccaro): study of collagen in the tissue and in chondrocytes cultured in agarose. ( 8160740 )
1994
4
A defect in the metabolic activation of sulfate in a patient with achondrogenesis type IB. ( 7977372 )
1994

Variations for Achondrogenesis, Type Ib

UniProtKB/Swiss-Prot genetic disease variations for Achondrogenesis, Type Ib:

75
# Symbol AA change Variation ID SNP ID
1 SLC26A2 p.Asn425Asp VAR_007437 rs104893920
2 SLC26A2 p.Gly678Val VAR_007438 rs104893916

ClinVar genetic disease variations for Achondrogenesis, Type Ib:

6 (show top 50) (show all 74)
# Gene Variation Type Significance SNP ID Assembly Location
1 SLC26A2 NM_000112.3(SLC26A2): c.1724delA (p.Lys575Serfs) deletion Pathogenic rs386833498 GRCh38 Chromosome 5, 149981317: 149981317
2 SLC26A2 NM_000112.3(SLC26A2): c.1724delA (p.Lys575Serfs) deletion Pathogenic rs386833498 GRCh37 Chromosome 5, 149360880: 149360880
3 SLC26A2 NM_000112.3(SLC26A2): c.391delC (p.Leu131Cysfs) deletion Likely pathogenic rs786200881 GRCh37 Chromosome 5, 149357606: 149357606
4 SLC26A2 NM_000112.3(SLC26A2): c.391delC (p.Leu131Cysfs) deletion Likely pathogenic rs786200881 GRCh38 Chromosome 5, 149978043: 149978043
5 SLC26A2 NM_000112.3(SLC26A2): c.835C> T (p.Arg279Trp) single nucleotide variant Pathogenic rs104893915 GRCh37 Chromosome 5, 149359991: 149359991
6 SLC26A2 NM_000112.3(SLC26A2): c.835C> T (p.Arg279Trp) single nucleotide variant Pathogenic rs104893915 GRCh38 Chromosome 5, 149980428: 149980428
7 SLC26A2 NM_000112.3(SLC26A2): c.532C> T (p.Arg178Ter) single nucleotide variant Pathogenic rs104893919 GRCh37 Chromosome 5, 149357747: 149357747
8 SLC26A2 NM_000112.3(SLC26A2): c.532C> T (p.Arg178Ter) single nucleotide variant Pathogenic rs104893919 GRCh38 Chromosome 5, 149978184: 149978184
9 SLC26A2 NM_000112.3(SLC26A2): c.1273A> G (p.Asn425Asp) single nucleotide variant Pathogenic rs104893920 GRCh37 Chromosome 5, 149360429: 149360429
10 SLC26A2 NM_000112.3(SLC26A2): c.1273A> G (p.Asn425Asp) single nucleotide variant Pathogenic rs104893920 GRCh38 Chromosome 5, 149980866: 149980866
11 SLC26A2 NM_000112.3(SLC26A2): c.2033G> T (p.Gly678Val) single nucleotide variant Likely pathogenic rs104893916 GRCh37 Chromosome 5, 149361189: 149361189
12 SLC26A2 NM_000112.3(SLC26A2): c.2033G> T (p.Gly678Val) single nucleotide variant Likely pathogenic rs104893916 GRCh38 Chromosome 5, 149981626: 149981626
13 SLC26A2 NM_000112.3(SLC26A2): c.1957T> A (p.Cys653Ser) single nucleotide variant Pathogenic/Likely pathogenic rs104893924 GRCh37 Chromosome 5, 149361113: 149361113
14 SLC26A2 NM_000112.3(SLC26A2): c.1957T> A (p.Cys653Ser) single nucleotide variant Pathogenic/Likely pathogenic rs104893924 GRCh38 Chromosome 5, 149981550: 149981550
15 SLC26A2 NM_000112.3(SLC26A2): c.1394delT (p.Leu465Cysfs) deletion Likely pathogenic rs386833495 GRCh37 Chromosome 5, 149360550: 149360550
16 SLC26A2 NM_000112.3(SLC26A2): c.1394delT (p.Leu465Cysfs) deletion Likely pathogenic rs386833495 GRCh38 Chromosome 5, 149980987: 149980987
17 SLC26A2 NM_000112.3(SLC26A2): c.1650delG (p.Ser551Valfs) deletion Conflicting interpretations of pathogenicity rs386833497 GRCh37 Chromosome 5, 149360806: 149360806
18 SLC26A2 NM_000112.3(SLC26A2): c.1650delG (p.Ser551Valfs) deletion Conflicting interpretations of pathogenicity rs386833497 GRCh38 Chromosome 5, 149981243: 149981243
19 SLC26A2 NM_000112.3(SLC26A2): c.1976delT (p.Leu659Terfs) deletion Likely pathogenic rs386833499 GRCh37 Chromosome 5, 149361132: 149361132
20 SLC26A2 NM_000112.3(SLC26A2): c.1976delT (p.Leu659Terfs) deletion Likely pathogenic rs386833499 GRCh38 Chromosome 5, 149981569: 149981569
21 SLC26A2 NM_000112.3(SLC26A2): c.1020_1022delTGT (p.Val341del) deletion Pathogenic/Likely pathogenic rs121908077 GRCh37 Chromosome 5, 149360176: 149360178
22 SLC26A2 NM_000112.3(SLC26A2): c.1020_1022delTGT (p.Val341del) deletion Pathogenic/Likely pathogenic rs121908077 GRCh38 Chromosome 5, 149980613: 149980615
23 SLC26A2 NM_000112.3(SLC26A2): c.1474C> T (p.Arg492Trp) single nucleotide variant Benign/Likely benign rs78676079 GRCh37 Chromosome 5, 149360630: 149360630
24 SLC26A2 NM_000112.3(SLC26A2): c.1474C> T (p.Arg492Trp) single nucleotide variant Benign/Likely benign rs78676079 GRCh38 Chromosome 5, 149981067: 149981067
25 SLC26A2 NM_000112.3(SLC26A2): c.1410A> G (p.Val470=) single nucleotide variant Benign/Likely benign rs115777661 GRCh37 Chromosome 5, 149360566: 149360566
26 SLC26A2 NM_000112.3(SLC26A2): c.1410A> G (p.Val470=) single nucleotide variant Benign/Likely benign rs115777661 GRCh38 Chromosome 5, 149981003: 149981003
27 SLC26A2 NM_000112.3(SLC26A2): c.229A> C (p.Asn77His) single nucleotide variant Benign rs76784312 GRCh37 Chromosome 5, 149357444: 149357444
28 SLC26A2 NM_000112.3(SLC26A2): c.229A> C (p.Asn77His) single nucleotide variant Benign rs76784312 GRCh38 Chromosome 5, 149977881: 149977881
29 SLC26A2 NM_000112.3(SLC26A2): c.1081G> A (p.Ala361Thr) single nucleotide variant Uncertain significance rs139051143 GRCh37 Chromosome 5, 149360237: 149360237
30 SLC26A2 NM_000112.3(SLC26A2): c.1081G> A (p.Ala361Thr) single nucleotide variant Uncertain significance rs139051143 GRCh38 Chromosome 5, 149980674: 149980674
31 SLC26A2 NM_000112.3(SLC26A2): c.1744C> T (p.Arg582Cys) single nucleotide variant Uncertain significance rs142542254 GRCh38 Chromosome 5, 149981337: 149981337
32 SLC26A2 NM_000112.3(SLC26A2): c.1744C> T (p.Arg582Cys) single nucleotide variant Uncertain significance rs142542254 GRCh37 Chromosome 5, 149360900: 149360900
33 SLC26A2 NM_000112.3(SLC26A2): c.185C> G (p.Ser62Ter) single nucleotide variant Likely pathogenic rs1057517523 GRCh37 Chromosome 5, 149357400: 149357400
34 SLC26A2 NM_000112.3(SLC26A2): c.185C> G (p.Ser62Ter) single nucleotide variant Likely pathogenic rs1057517523 GRCh38 Chromosome 5, 149977837: 149977837
35 SLC26A2 NM_000112.3(SLC26A2): c.188delA (p.Asp63Valfs) deletion Likely pathogenic rs1057517496 GRCh38 Chromosome 5, 149977840: 149977840
36 SLC26A2 NM_000112.3(SLC26A2): c.188delA (p.Asp63Valfs) deletion Likely pathogenic rs1057517496 GRCh37 Chromosome 5, 149357403: 149357403
37 SLC26A2 NM_000112.3(SLC26A2): c.207delT (p.Phe69Leufs) deletion Likely pathogenic rs1057517462 GRCh38 Chromosome 5, 149977859: 149977859
38 SLC26A2 NM_000112.3(SLC26A2): c.207delT (p.Phe69Leufs) deletion Likely pathogenic rs1057517462 GRCh37 Chromosome 5, 149357422: 149357422
39 SLC26A2 NM_000112.3(SLC26A2): c.239_243dupGCAGT (p.Pro82Alafs) duplication Likely pathogenic rs1057517504 GRCh38 Chromosome 5, 149977891: 149977895
40 SLC26A2 NM_000112.3(SLC26A2): c.239_243dupGCAGT (p.Pro82Alafs) duplication Likely pathogenic rs1057517504 GRCh37 Chromosome 5, 149357454: 149357458
41 SLC26A2 NM_000112.3(SLC26A2): c.485_486delTG (p.Val162Glyfs) deletion Likely pathogenic rs1057517527 GRCh37 Chromosome 5, 149357700: 149357701
42 SLC26A2 NM_000112.3(SLC26A2): c.485_486delTG (p.Val162Glyfs) deletion Likely pathogenic rs1057517527 GRCh38 Chromosome 5, 149978137: 149978138
43 SLC26A2 NM_000112.3(SLC26A2): c.541C> T (p.Gln181Ter) single nucleotide variant Likely pathogenic rs1057517483 GRCh38 Chromosome 5, 149978193: 149978193
44 SLC26A2 NM_000112.3(SLC26A2): c.541C> T (p.Gln181Ter) single nucleotide variant Likely pathogenic rs1057517483 GRCh37 Chromosome 5, 149357756: 149357756
45 SLC26A2 NM_000112.3(SLC26A2): c.699+2T> C single nucleotide variant Pathogenic rs1057517461 GRCh38 Chromosome 5, 149978353: 149978353
46 SLC26A2 NM_000112.3(SLC26A2): c.699+2T> C single nucleotide variant Pathogenic rs1057517461 GRCh37 Chromosome 5, 149357916: 149357916
47 SLC26A2 NM_000112.3(SLC26A2): c.736_739delGTCT (p.Val246Thrfs) deletion Likely pathogenic rs1057517524 GRCh37 Chromosome 5, 149359892: 149359895
48 SLC26A2 NM_000112.3(SLC26A2): c.736_739delGTCT (p.Val246Thrfs) deletion Likely pathogenic rs1057517524 GRCh38 Chromosome 5, 149980329: 149980332
49 SLC26A2 NM_000112.3(SLC26A2): c.746C> G (p.Ser249Ter) single nucleotide variant Likely pathogenic rs1057517514 GRCh38 Chromosome 5, 149980339: 149980339
50 SLC26A2 NM_000112.3(SLC26A2): c.746C> G (p.Ser249Ter) single nucleotide variant Likely pathogenic rs1057517514 GRCh37 Chromosome 5, 149359902: 149359902

Expression for Achondrogenesis, Type Ib

Search GEO for disease gene expression data for Achondrogenesis, Type Ib.

Pathways for Achondrogenesis, Type Ib

Pathways related to Achondrogenesis, Type Ib according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.71 BGN DCN
2 10.18 BGN DCN

GO Terms for Achondrogenesis, Type Ib

Cellular components related to Achondrogenesis, Type Ib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi lumen GO:0005796 9.26 BGN DCN
2 lysosomal lumen GO:0043202 9.16 BGN DCN
3 brush border membrane GO:0031526 8.96 SLC26A3 SLC26A4
4 apical plasma membrane GO:0016324 8.8 SLC26A2 SLC26A3 SLC26A4

Biological processes related to Achondrogenesis, Type Ib according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 transmembrane transport GO:0055085 9.81 SLC26A2 SLC26A3 SLC26A4 SLC26A5
2 regulation of membrane potential GO:0042391 9.67 SLC26A2 SLC26A3 SLC26A4 SLC26A5
3 chloride transmembrane transport GO:1902476 9.62 SLC26A2 SLC26A3 SLC26A4 SLC26A5
4 anion transmembrane transport GO:0098656 9.58 SLC26A3 SLC26A4 SLC26A5
5 bicarbonate transport GO:0015701 9.56 SLC26A2 SLC26A3 SLC26A4 SLC26A5
6 skeletal muscle tissue development GO:0007519 9.54 DCN FLNB
7 chondroitin sulfate biosynthetic process GO:0030206 9.52 BGN DCN
8 chondroitin sulfate catabolic process GO:0030207 9.49 BGN DCN
9 dermatan sulfate biosynthetic process GO:0030208 9.48 BGN DCN
10 positive regulation of mitochondrial depolarization GO:0051901 9.46 CCK DCN
11 sulfate transport GO:0008272 9.46 SLC26A2 SLC26A3 SLC26A4 SLC26A5
12 peptide cross-linking via chondroitin 4-sulfate glycosaminoglycan GO:0019800 9.43 BGN DCN
13 sulfate transmembrane transport GO:1902358 9.26 SLC26A2 SLC26A3 SLC26A4 SLC26A5
14 oxalate transport GO:0019532 8.92 SLC26A2 SLC26A3 SLC26A4 SLC26A5

Molecular functions related to Achondrogenesis, Type Ib according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 anion:anion antiporter activity GO:0015301 9.67 SLC26A2 SLC26A3 SLC26A4 SLC26A5
2 sulfate transmembrane transporter activity GO:0015116 9.62 SLC26A2 SLC26A3 SLC26A4 SLC26A5
3 bicarbonate transmembrane transporter activity GO:0015106 9.56 SLC26A2 SLC26A3 SLC26A4 SLC26A5
4 extracellular matrix binding GO:0050840 9.46 BGN DCN
5 chloride transmembrane transporter activity GO:0015108 9.46 SLC26A2 SLC26A3 SLC26A4 SLC26A5
6 glycosaminoglycan binding GO:0005539 9.43 BGN DCN
7 extracellular matrix structural constituent conferring compression resistance GO:0030021 9.4 BGN DCN
8 secondary active sulfate transmembrane transporter activity GO:0008271 9.26 SLC26A2 SLC26A3 SLC26A4 SLC26A5
9 oxalate transmembrane transporter activity GO:0019531 8.92 SLC26A2 SLC26A3 SLC26A4 SLC26A5

Sources for Achondrogenesis, Type Ib

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
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49 NCI
50 NCIt
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54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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