GPHYSD1
MCID: GLP003
MIFTS: 33

Geleophysic Dysplasia 1 (GPHYSD1)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Liver diseases, Rare diseases, Respiratory diseases, Skin diseases, Smell/Taste diseases

Aliases & Classifications for Geleophysic Dysplasia 1

MalaCards integrated aliases for Geleophysic Dysplasia 1:

Name: Geleophysic Dysplasia 1 57 74 29 13 6 72
Gphysd1 57 74
Geleophysic Dysplasia 72
Geleophysic Dwarfism 74

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
lysosomal storage vacuoles in trachea, liver, cartilage, and heart


HPO:

32
geleophysic dysplasia 1:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

MeSH 44 D004392
MedGen 42 C3278147
UMLS 72 C3278147 C3489726

Summaries for Geleophysic Dysplasia 1

OMIM : 57 Geleophysic dysplasia-1 is an autosomal recessive disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. 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 progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues (summary by Le Goff et al., 2011). (231050)

MalaCards based summary : Geleophysic Dysplasia 1, also known as gphysd1, is related to geleophysic dwarfism and geleophysic dysplasia, and has symptoms including seizures and thick skin. An important gene associated with Geleophysic Dysplasia 1 is ADAMTSL2 (ADAMTS Like 2). Affiliated tissues include skin, bone and heart, and related phenotypes are pectus excavatum and osteopenia

UniProtKB/Swiss-Prot : 74 Geleophysic dysplasia 1: An autosomal recessive disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. 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 progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues.

Related Diseases for Geleophysic Dysplasia 1

Diseases in the Geleophysic Dysplasia family:

Geleophysic Dysplasia 1 Geleophysic Dysplasia 2
Geleophysic Dysplasia 3

Diseases related to Geleophysic Dysplasia 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 geleophysic dwarfism 12.5
2 geleophysic dysplasia 11.9
3 geleophysic dysplasia 2 11.4
4 chromosome 8q22.1 duplication syndrome 11.3
5 dwarfism 10.3
6 mucopolysaccharidosis-plus syndrome 10.2

Graphical network of the top 20 diseases related to Geleophysic Dysplasia 1:



Diseases related to Geleophysic Dysplasia 1

Symptoms & Phenotypes for Geleophysic Dysplasia 1

Human phenotypes related to Geleophysic Dysplasia 1:

32 (show all 35)
# Description HPO Frequency HPO Source Accession
1 pectus excavatum 32 HP:0000767
2 osteopenia 32 HP:0000938
3 seizures 32 HP:0001250
4 global developmental delay 32 HP:0001263
5 hepatomegaly 32 HP:0002240
6 joint stiffness 32 HP:0001387
7 short nose 32 HP:0003196
8 smooth philtrum 32 HP:0000319
9 anteverted nares 32 HP:0000463
10 short stature 32 HP:0004322
11 long philtrum 32 HP:0000343
12 coxa valga 32 HP:0002673
13 short palm 32 HP:0004279
14 congestive heart failure 32 HP:0001635
15 short long bone 32 HP:0003026
16 lack of skin elasticity 32 HP:0100679
17 short foot 32 HP:0001773
18 thickened skin 32 HP:0001072
19 wide mouth 32 HP:0000154
20 small nail 32 HP:0001792
21 upslanted palpebral fissure 32 HP:0000582
22 round face 32 HP:0000311
23 tracheal stenosis 32 HP:0002777
24 thickened helices 32 HP:0000391
25 high pitched voice 32 HP:0001620
26 camptodactyly of finger 32 HP:0100490
27 wrist flexion contracture 32 HP:0001239
28 aortic valve stenosis 32 HP:0001650
29 mitral stenosis 32 HP:0001718
30 j-shaped sella turcica 32 HP:0002680
31 joint contracture of the hand 32 HP:0009473
32 irregular capital femoral epiphysis 32 HP:0005041
33 tricuspid stenosis 32 HP:0010446
34 hypoplasia of the capital femoral epiphysis 32 HP:0003090
35 short metacarpals with rounded proximal ends 32 HP:0006161

Symptoms via clinical synopsis from OMIM:

57
Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Neurologic Central Nervous System:
seizures
developmental delay

Head And Neck Nose:
short nose
anteverted nares

Skeletal Pelvis:
coxa valga

Head And Neck Mouth:
wide mouth

Head And Neck Ears:
thickened helices

Skeletal Skull:
j-shaped sella turcica

Growth Weight:
normal birth weight

Skeletal Feet:
short feet
short, plump tubular bones

Voice:
high-pitched voice

Head And Neck Face:
long, smooth philtrum
round, full face
'pleasant, happy-nature' appearance

Head And Neck Head:
normal head circumference

Skeletal:
osteopenia

Abdomen Liver:
hepatomegaly

Growth Height:
short stature
normal upper/lower segment ratio

Skin Nails Hair Skin:
thickened skin
tight skin

Respiratory Airways:
tracheal stenosis
brainstem bronchi stenosis

Cardiovascular Heart:
mitral stenosis
tricuspid stenosis
cardiac failure

Skeletal Hands:
short metacarpals with rounded proximal ends
short hands
wrist contractures
finger contractures

Skeletal Limbs:
shortened long tubular bones
small, irregular capital femoral epiphyses

Cardiovascular Vascular:
aortic stenosis

Skin Nails Hair Nails:
small nails

Head And Neck Eyes:
upward slanting palpebral fissures

Clinical features from OMIM:

231050

UMLS symptoms related to Geleophysic Dysplasia 1:


seizures, thick skin

Drugs & Therapeutics for Geleophysic Dysplasia 1

Search Clinical Trials , NIH Clinical Center for Geleophysic Dysplasia 1

Genetic Tests for Geleophysic Dysplasia 1

Genetic tests related to Geleophysic Dysplasia 1:

# Genetic test Affiliating Genes
1 Geleophysic Dysplasia 1 29 ADAMTSL2

Anatomical Context for Geleophysic Dysplasia 1

MalaCards organs/tissues related to Geleophysic Dysplasia 1:

41
Skin, Bone, Heart, Trachea, Liver, Eye

Publications for Geleophysic Dysplasia 1

Articles related to Geleophysic Dysplasia 1:

(show top 50) (show all 61)
# Title Authors PMID Year
1
Geleophysic dysplasia: 48 year clinical update with emphasis on cardiac care. 38 8 71
30195254 2018
2
Novel mutations in ADAMTSL2 gene underlying geleophysic dysplasia in families from United Arab Emirates. 38 8 71
24014090 2013
3
Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia. 38 8 71
21415077 2011
4
Geleophysic Dysplasia 38 71
20301776 2009
5
ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. 38 8
18677313 2008
6
Geleophysic dysplasia: 7-year follow-up study of a patient with an intermediate form. 38 8
10440835 1999
7
Patients with geleophysic dysplasia are not always geleophysic. 38 8
9295082 1997
8
Clinical and ultrastructural findings in three patients with geleophysic dysplasia. 38 8
8723086 1996
9
Geleophysic dysplasia: a report of three affected boys--prenatal ultrasound does not detect recurrence. 38 8
8533820 1995
10
Geleophysic dysplasia: a storage disorder affecting the skin, bone, liver, heart, and trachea. 38 8
2380821 1990
11
Geleophysic dysplasia. 38 8
2090119 1990
12
Geleophysic dysplasia. 38 8
6507495 1984
13
Familial recurrence of geleophysic dysplasia. 38 8
6507494 1984
14
Acrofacial dysplasia resembling geleophysic dysplasia. 38 8
6507496 1984
15
Mutations in the TGFβ binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. 8
21683322 2011
16
Geleophysic dwarfism--a "focal" mucopolysaccharidosis? 8
4104008 1971
17
Mitral stenosis in an atypical case of gargoylism: a case report with pathologic and histochemical studies of the cardiac tissues. 8
13841169 1960
18
Optic disc swelling in acromicric and geleophysic dysplasia. 38
31228225 2019
19
Skin fibroblasts of patients with geleophysic dysplasia due to FBN1 mutations have lysosomal inclusions and losartan improves their microfibril deposition defect. 38
31350823 2019
20
Genotype-phenotype correlation and expansion of orodental anomalies in LTBP3-related disorders. 38
30887145 2019
21
Accommodative esotropia and Brown syndrome in a girl with recessive geleophysic dysplasia. 38
30415012 2019
22
Limb- and tendon-specific Adamtsl2 deletion identifies a role for ADAMTSL2 in tendon growth in a mouse model for geleophysic dysplasia. 38
30738849 2019
23
Impairment of chondrogenesis and microfibrillar network in Adamtsl2 deficiency. 38
30303737 2019
24
A report of three families with FBN1-related acromelic dysplasias and review of literature for genotype-phenotype correlation in geleophysic dysplasia. 38
29191498 2018
25
The Clinical Cases of Geleophysic Dysplasia: One Gene, Different Phenotypes. 38
30057829 2018
26
A chinese boy with geleophysic dysplasia caused by compound heterozygous mutations in ADAMTSL2. 38
28917829 2017
27
Rapidly progressive mitral valve stenosis in patients with acromelic dysplasia. 38
28077185 2017
28
Clinical Phenotype of Musladin-Lueke Syndrome in 2 Beagles. 38
28158899 2017
29
Three cases of Japanese acromicric/geleophysic dysplasia with FBN1 mutations: a comparison of clinical and radiological features. 38
27935852 2017
30
Novel ADAMTSL2-mutations in a patient with geleophysic dysplasia type I. 38
27057656 2016
31
Mutations in LTBP3 cause acromicric dysplasia and geleophysic dysplasia. 38
27068007 2016
32
Skeletal manifestations of Marfan syndrome associated to heterozygous R2726W FBN1 variant: sibling case report and literature review. 38
26875674 2016
33
Two Patients with Severe Short Stature due to a FBN1 Mutation (p.Ala1728Val) with a Mild Form of Acromicric Dysplasia. 38
27245183 2016
34
ADAMTS proteins as modulators of microfibril formation and function. 38
25957949 2015
35
Geleophysic dysplasia: a novel in-frame deletion of a tandem repeat in the ADAMTSL2 gene. 38
25850559 2015
36
Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia--a novel mouse model providing insights into geleophysic dysplasia. 38
25762570 2015
37
Cardiac involvement in geleophysic dysplasia in three siblings of a Saudi family. 38
24192049 2015
38
Children with short-limbed short stature in pediatric endocrinological services in Japan. 38
25244068 2014
39
Three novel mutations of the FBN1 gene in Chinese children with acromelic dysplasia. 38
25142510 2014
40
Novel mutations in geleophysic dysplasia type 1. 38
24251637 2014
41
Similarity of geleophysic dysplasia and Weill-Marchesani syndrome. 38
24214363 2013
42
More than meets the eye: The evolving phenotype of Weill-Marchesani syndrome-diagnostic confusion with geleophysic dysplasia. 38
24039088 2013
43
Missense mutations in FBN1 exons 41 and 42 cause Weill-Marchesani syndrome with thoracic aortic disease and Marfan syndrome. 38
23897642 2013
44
Geleophysic dysplasia associated with bilateral angle closure glaucoma. 38
23514648 2013
45
A Japanese child with geleophysic dysplasia caused by a novel mutation of FBN1. 38
23124041 2013
46
From tall to short: the role of TGFβ signaling in growth and its disorders. 38
22791552 2012
47
Genetic and functional linkage between ADAMTS superfamily proteins and fibrillin-1: a novel mechanism influencing microfibril assembly and function. 38
21858451 2011
48
An ADAMTSL2 founder mutation causes Musladin-Lueke Syndrome, a heritable disorder of beagle dogs, featuring stiff skin and joint contractures. 38
20862248 2010
49
Genetic and molecular aspects of acromelic dysplasia. 38
19396027 2009
50
Clinical and morphological phenotype of geleophysic dysplasia. 38
18510828 2008

Variations for Geleophysic Dysplasia 1

ClinVar genetic disease variations for Geleophysic Dysplasia 1:

6 (show all 20)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.440C> T (p.Pro147Leu) single nucleotide variant Pathogenic rs113994121 9:136405747-136405747 9:133540625-133540625
2 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.338G> A (p.Arg113His) single nucleotide variant Pathogenic rs113994122 9:136404921-136404921 9:133539799-133539799
3 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.340G> A (p.Glu114Lys) single nucleotide variant Pathogenic rs113994123 9:136404923-136404923 9:133539801-133539801
4 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.2431G> A (p.Gly811Arg) single nucleotide variant Pathogenic rs113994124 9:136435468-136435468 9:133570346-133570346
5 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.2586G> A (p.Trp862Ter) single nucleotide variant Pathogenic rs113994125 9:136435623-136435623 9:133570501-133570501
6 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.215G> A (p.Arg72Gln) single nucleotide variant Pathogenic rs387907064 9:136402651-136402651 9:133537529-133537529
7 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.661C> T (p.Arg221Cys) single nucleotide variant Pathogenic rs387907065 9:136406102-136406102 9:133540980-133540980
8 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.234-2A> G single nucleotide variant Pathogenic rs775621284 9:136403469-136403469 9:133538347-133538347
9 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.499G> A (p.Asp167Asn) single nucleotide variant Pathogenic 9:136405806-136405806 9:133540684-133540684
10 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.493G> A (p.Ala165Thr) single nucleotide variant Uncertain significance rs764516811 9:136405800-136405800 9:133540678-133540678
11 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.1641C> T (p.His547=) single nucleotide variant Uncertain significance rs7868941 9:136421044-136421044 9:133555922-133555922
12 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.2613G> A (p.Val871=) single nucleotide variant Uncertain significance rs62637566 9:136438985-136438985 9:133573863-133573863
13 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.2717C> T (p.Pro906Leu) single nucleotide variant Uncertain significance rs969732840 9:136439089-136439089 9:133573967-133573967
14 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.2022C> T (p.Pro674=) single nucleotide variant Likely benign rs534165083 9:136433542-136433542 9:133568420-133568420
15 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.2313A> G (p.Val771=) single nucleotide variant Benign rs1064975 9:136434598-136434598 9:133569476-133569476
16 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.683-12T> G single nucleotide variant Benign rs9802778 9:136409580-136409580 9:133544458-133544458
17 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.840A> T (p.Ala280=) single nucleotide variant Benign rs2073875 9:136412236-136412236 9:133547114-133547114
18 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.859A> C (p.Arg287=) single nucleotide variant Benign rs2073876 9:136412255-136412255 9:133547133-133547133
19 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.774C> T (p.Asp258=) single nucleotide variant Benign rs2073874 9:136412170-136412170 9:133547048-133547048
20 ADAMTSL2 NM_001145320.1(ADAMTSL2): c.939+11C> T single nucleotide variant Benign rs2073878 9:136412346-136412346 9:133547224-133547224

UniProtKB/Swiss-Prot genetic disease variations for Geleophysic Dysplasia 1:

74 (show all 14)
# Symbol AA change Variation ID SNP ID
1 ADAMTSL2 p.Arg113His VAR_054874 rs113994122
2 ADAMTSL2 p.Glu114Lys VAR_054875 rs113994123
3 ADAMTSL2 p.Pro147Leu VAR_054876 rs113994121
4 ADAMTSL2 p.Gly811Arg VAR_054877 rs113994124
5 ADAMTSL2 p.Trp50Cys VAR_066543 rs139521976
6 ADAMTSL2 p.Arg72Gln VAR_066544 rs387907064
7 ADAMTSL2 p.Arg159Trp VAR_066545 rs776178041
8 ADAMTSL2 p.Ala165Thr VAR_066546 rs764516811
9 ADAMTSL2 p.Cys171Arg VAR_066547
10 ADAMTSL2 p.Arg221Cys VAR_066548 rs387907065
11 ADAMTSL2 p.Ala239Thr VAR_066549
12 ADAMTSL2 p.Arg593Cys VAR_066551
13 ADAMTSL2 p.Ser635Leu VAR_066552
14 ADAMTSL2 p.Pro906Leu VAR_066553 rs969732840

Expression for Geleophysic Dysplasia 1

Search GEO for disease gene expression data for Geleophysic Dysplasia 1.

Pathways for Geleophysic Dysplasia 1

GO Terms for Geleophysic Dysplasia 1

Sources for Geleophysic Dysplasia 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
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33 ICD10
34 ICD10 via Orphanet
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38 LifeMap
40 LOVD
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44 MeSH
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58 OMIM via Orphanet
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64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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