GPHYSD3
MCID: GLP007
MIFTS: 33

Geleophysic Dysplasia 3 (GPHYSD3)

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

Aliases & Classifications for Geleophysic Dysplasia 3

MalaCards integrated aliases for Geleophysic Dysplasia 3:

Name: Geleophysic Dysplasia 3 57 12 72 29 6 15
Gphysd3 57 12 72

Characteristics:

OMIM®:

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

Miscellaneous:
based on report of a family and 2 unrelated patients (last curated december 2017)
early death due to respiratory failure (in some patients)


HPO:

31
geleophysic dysplasia 3:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Geleophysic Dysplasia 3

UniProtKB/Swiss-Prot : 72 Geleophysic dysplasia 3: A form of geleophysic dysplasia, a rare skeletal disease characterized by severe short stature, short hands and feet, and joint limitations. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include skin thickening, progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues. GPHYSD3 inheritance is autosomal dominant.

MalaCards based summary : Geleophysic Dysplasia 3, also known as gphysd3, is related to excessive tearing and witkop syndrome. An important gene associated with Geleophysic Dysplasia 3 is LTBP3 (Latent Transforming Growth Factor Beta Binding Protein 3), and among its related pathways/superpathways are Phospholipase-C Pathway and p70S6K Signaling. Affiliated tissues include bone, and related phenotypes are polyhydramnios and long philtrum

Disease Ontology : 12 A geleophysic dysplasia that has material basis in heterozygous mutation in LTBP3 on chromosome 11q13.1.

More information from OMIM: 617809 PS231050

Related Diseases for Geleophysic Dysplasia 3

Diseases in the Geleophysic Dysplasia family:

Geleophysic Dysplasia 1 Geleophysic Dysplasia 2
Geleophysic Dysplasia 3

Diseases related to Geleophysic Dysplasia 3 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 28)
# Related Disease Score Top Affiliating Genes
1 excessive tearing 10.0 LTBP3 LTBP2
2 witkop syndrome 10.0 LTBP3 LTBP2
3 hydrophthalmos 10.0 LTBP3 LTBP2
4 phacogenic glaucoma 10.0 LTBP3 LTBP2
5 autosomal recessive cutis laxa type i 10.0 LTBP3 LTBP2
6 brachyolmia 10.0 LTBP3 LTBP2
7 megalocornea 10.0 LTBP3 LTBP2
8 camurati-engelmann disease 10.0 LTBP3 LTBP2
9 iris disease 10.0 LTBP3 LTBP2
10 juvenile glaucoma 10.0 LTBP3 LTBP2
11 lens subluxation 10.0 LTBP2 ADAMTSL2
12 primary congenital glaucoma 9.9 LTBP3 LTBP2
13 glaucoma 3, primary congenital, a 9.9 LTBP3 LTBP2
14 aortic aneurysm, familial thoracic 1 9.9 LTBP3 LTBP2
15 axenfeld-rieger syndrome 9.9 LTBP3 LTBP2
16 tracheal disease 9.8 TBRG1 ADAMTSL2
17 aniridia 1 9.8 LTBP3 LTBP2
18 anterior segment dysgenesis 9.8 LTBP3 LTBP2 ADAMTSL2
19 glaucoma, primary open angle 9.7 LTBP3 LTBP2
20 tracheal stenosis 9.6 TBRG1 LTBP3 ADAMTSL2
21 stiff skin syndrome 9.6 TBRG1 LTBP3 ADAMTSL2
22 peters-plus syndrome 9.5 TSR1 LTBP3 LTBP2 ADAMTSL2
23 acromicric dysplasia 9.4 TBRG1 LTBP3 LTBP2 ADAMTSL2
24 isolated ectopia lentis 9.4 TBRG1 LTBP3 LTBP2 ADAMTSL2
25 weill-marchesani syndrome 9.4 TBRG1 LTBP3 LTBP2 ADAMTSL2
26 geleophysic dysplasia 1 9.0 TSR2 TBRG1 LTBP3 LTBP2 ADAMTSL2
27 geleophysic dysplasia 8.8 TSR2 TSR1 TBRG1 LTBP3 LTBP2 ADAMTSL2
28 geleophysic dysplasia 2 8.7 TSR2 TSR1 TBRG1 LTBP3 LTBP2 ADAMTSL2

Graphical network of the top 20 diseases related to Geleophysic Dysplasia 3:



Diseases related to Geleophysic Dysplasia 3

Symptoms & Phenotypes for Geleophysic Dysplasia 3

Human phenotypes related to Geleophysic Dysplasia 3:

31 (show all 23)
# Description HPO Frequency HPO Source Accession
1 polyhydramnios 31 very rare (1%) HP:0001561
2 long philtrum 31 very rare (1%) HP:0000343
3 sleep apnea 31 HP:0010535
4 hepatomegaly 31 HP:0002240
5 delayed skeletal maturation 31 HP:0002750
6 depressed nasal bridge 31 HP:0005280
7 wide nasal bridge 31 HP:0000431
8 thick vermilion border 31 HP:0012471
9 anteverted nares 31 HP:0000463
10 short stature 31 HP:0004322
11 epiphyseal dysplasia 31 HP:0002656
12 dyspnea 31 HP:0002094
13 brachydactyly 31 HP:0001156
14 bulbous nose 31 HP:0000414
15 hoarse voice 31 HP:0001609
16 round face 31 HP:0000311
17 respiratory failure 31 HP:0002878
18 short foot 31 HP:0001773
19 thickened skin 31 HP:0001072
20 pneumonia 31 HP:0002090
21 tracheal stenosis 31 HP:0002777
22 limb undergrowth 31 HP:0009826
23 subglottic stenosis 31 HP:0001607

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Respiratory Nasopharynx:
sleep apnea

Head And Neck Nose:
depressed nasal bridge
anteverted nares
bulbous nose
broad nasal bridge

Respiratory:
dyspnea

Head And Neck Face:
round face
long philtrum (in some patients)

Respiratory Airways:
tracheal stenosis

Skin Nails Hair Skin:
thick skin

Muscle Soft Tissue:
pseudomuscular build

Head And Neck Mouth:
thick lips

Skeletal Feet:
short feet

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (in some patients)

Abdomen Liver:
hepatomegaly

Growth Height:
short stature

Voice:
hoarse voice

Respiratory Lung:
respiratory failure
alveolointerstitial pneumonia

Respiratory Larynx:
subglottic stenosis

Cardiovascular Vascular:
pulmonary hypertension

Head And Neck Eyes:
well-defined eyebrows

Skeletal:
delayed bone age

Skeletal Limbs:
short limbs
limited movement at elbows
limited movement at wrists
epiphyseal dysplasia of proximal femur

Skeletal Hands:
marked brachydactyly
difficulty making a fist
external notch on second metacarpal
internal notch on fifth metacarpal

Clinical features from OMIM®:

617809 (Updated 05-Apr-2021)

Drugs & Therapeutics for Geleophysic Dysplasia 3

Search Clinical Trials , NIH Clinical Center for Geleophysic Dysplasia 3

Genetic Tests for Geleophysic Dysplasia 3

Genetic tests related to Geleophysic Dysplasia 3:

# Genetic test Affiliating Genes
1 Geleophysic Dysplasia 3 29 LTBP3

Anatomical Context for Geleophysic Dysplasia 3

MalaCards organs/tissues related to Geleophysic Dysplasia 3:

40
Bone

Publications for Geleophysic Dysplasia 3

Articles related to Geleophysic Dysplasia 3:

# Title Authors PMID Year
1
Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia. 6 57
27068007 2016
2
Geleophysic dysplasia: novel missense variants and insights into ADAMTSL2 intracellular trafficking. 61
31516831 2019
3
Genotype-phenotype correlation and expansion of orodental anomalies in LTBP3-related disorders. 61
30887145 2019

Variations for Geleophysic Dysplasia 3

ClinVar genetic disease variations for Geleophysic Dysplasia 3:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LTBP3 NM_021070.4(LTBP3):c.1846+5G>A SNV Pathogenic 448913 rs1188540819 GRCh37: 11:65315386-65315386
GRCh38: 11:65547915-65547915
2 LTBP3 NM_021070.4(LTBP3):c.3771A>T (p.Ter1257Cys) SNV Pathogenic 448912 rs1554971742 GRCh37: 11:65306551-65306551
GRCh38: 11:65539080-65539080
3 LTBP3 NM_021070.4(LTBP3):c.2087C>G (p.Ser696Cys) SNV Uncertain significance 448911 rs1554974135 GRCh37: 11:65314930-65314930
GRCh38: 11:65547459-65547459
4 LTBP3 NM_021070.4(LTBP3):c.989C>T (p.Pro330Leu) SNV Uncertain significance 548546 rs28403592 GRCh37: 11:65320709-65320709
GRCh38: 11:65553238-65553238

Expression for Geleophysic Dysplasia 3

Search GEO for disease gene expression data for Geleophysic Dysplasia 3.

Pathways for Geleophysic Dysplasia 3

Pathways related to Geleophysic Dysplasia 3 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.5 TBRG1 LTBP3 LTBP2
2
Show member pathways
12.46 TBRG1 LTBP3 LTBP2
3
Show member pathways
11.95 TBRG1 LTBP3 LTBP2
4
Show member pathways
11.79 TBRG1 LTBP3 LTBP2
5
Show member pathways
11.34 TBRG1 LTBP3 LTBP2
6
Show member pathways
11.12 LTBP3 LTBP2
7 10.49 TBRG1 LTBP3 LTBP2
8 10.45 TBRG1 LTBP3 LTBP2

GO Terms for Geleophysic Dysplasia 3

Biological processes related to Geleophysic Dysplasia 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transforming growth factor beta receptor signaling pathway GO:0007179 8.96 LTBP3 LTBP2
2 maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) GO:0000462 8.62 TSR2 TSR1

Molecular functions related to Geleophysic Dysplasia 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 growth factor binding GO:0019838 8.96 LTBP3 LTBP2
2 microfibril binding GO:0050436 8.62 LTBP2 ADAMTSL2

Sources for Geleophysic Dysplasia 3

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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