TD1
MCID: THN009
MIFTS: 62

Thanatophoric Dysplasia, Type I (TD1)

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

Aliases & Classifications for Thanatophoric Dysplasia, Type I

MalaCards integrated aliases for Thanatophoric Dysplasia, Type I:

Name: Thanatophoric Dysplasia, Type I 56 13 71
Thanatophoric Dysplasia 56 12 74 24 52 25 58 36 54 43 15
Thanatophoric Dysplasia Type 1 52 58 29 6
Thanatophoric Dwarfism 56 52 25 73
Td1 56 52 58 73
Td 56 52 58
Thanatophoric Dysplasia Type I 52 73
Thanatophoric Dwarfism Type 1 52 58
Thanatophoric Short Stature 25 32
Lethal Short-Limbed Platyspondylic Dwarfism, San Diego Type 56
Lethal Short-Limbed Platyspondylic Dwarfism San Diego Type 73
Platyspondylic Lethal Skeletal Dysplasia, San Diego Type 56
Platyspondylic Lethal Skeletal Dysplasia San Diego Type 73
Dysplasia, Thanatophoric, Type I 39
Thanatophoric Dysplasia; Td 56
Thanatophoric Dysplasia 1 73
Thanatophoric Dwarfism 1 52
Dwarfism Thanatophoric 52
Dwarf, Thanatophoric 25

Characteristics:

Orphanet epidemiological data:

58
thanatophoric dysplasia
Inheritance: Autosomal dominant,Not applicable; Prevalence: 1-9/100000 (Europe); Age of onset: Antenatal,Neonatal; Age of death: early childhood;
thanatophoric dysplasia type 1
Inheritance: Autosomal dominant,Not applicable; Age of onset: Antenatal,Neonatal; Age of death: stillbirth;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
death in majority of infants soon after birth


HPO:

31
thanatophoric dysplasia, type i:
Clinical modifier neonatal death
Inheritance autosomal dominant inheritance


GeneReviews:

24
Penetrance The penetrance of fgfr3 pathogenic variants is 100%.

Classifications:

Orphanet: 58  
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Thanatophoric Dysplasia, Type I

NIH Rare Diseases : 52 Thanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra skin on the arms and legs. Other features of this condition include a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. Most infants with thanatophoric dysplasia are stillborn or die shortly after birth from respiratory failure. A few affected individuals have survived into childhood with extensive medical help. Thanatophoric dysplasia is caused by mutations in the FGFR3 gene . While this condition is considered to be autosomal dominant , virtually all cases have occurred in people with no history of the disorder in their family. Two major forms of thanatophoric dysplasia have been described, type I and type II. Type I thanatophoric dysplasia is distinguished by the presence of curved thigh bones and flattened bones of the spine (platyspondyly). Type II thanatophoric dysplasia is characterized by straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull.

MalaCards based summary : Thanatophoric Dysplasia, Type I, also known as thanatophoric dysplasia, is related to thanatophoric dysplasia, type ii and nevus, epidermal. An important gene associated with Thanatophoric Dysplasia, Type I is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are Signaling by GPCR and Innate Immune System. Affiliated tissues include bone, skin and lung, and related phenotypes are macrocephaly and muscular hypotonia

Disease Ontology : 12 An osteochondrodysplasia that results in short arms and legs with excess folds of skin.

Genetics Home Reference : 25 Thanatophoric dysplasia is a severe skeletal disorder characterized by extremely short limbs and folds of extra (redundant) skin on the arms and legs. Other features of this condition include a narrow chest, short ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. Researchers have described two major forms of thanatophoric dysplasia, type I and type II. Type I thanatophoric dysplasia is distinguished by the presence of curved thigh bones and flattened bones of the spine (platyspondyly). Type II thanatophoric dysplasia is characterized by straight thigh bones and a moderate to severe skull abnormality called a cloverleaf skull. The term thanatophoric is Greek for "death bearing." Infants with thanatophoric dysplasia are usually stillborn or die shortly after birth from respiratory failure; however, a few affected individuals have survived into childhood with extensive medical help.

OMIM : 56 Thanatophoric dysplasia is a severe short-limb dwarfism syndrome that is usually lethal in the perinatal period. Norman et al. (1992) classified cases of TD into subtypes based on the presence of curved as opposed to straight femurs; patients with straight, relatively long femurs always had associated severe cloverleaf skull and were designated TD type II (TD2), while TD cases with curved, short femurs with or without cloverleaf skull were designated TD type I (TD1) (Langer et al., 1987). (187600)

KEGG : 36 Thanatophoric dysplasia (TD) is a congenital skeletal dysplasia characterized by marked underdevelopment of the skeletal system and short-limb dwarfism. It is the most common form of lethal skeletal dysplasia syndromes. Two types of TD have been described. Type I TD (TDI) is associated with curved and short femurs. The shortness of the bones in type II TD (TDII) is not as significant as in TDI. TDII is characterized by straight femurs and cloverleaf skull deformity. Other features common to type I and type II include short ribs, narrow thorax, macrocephaly, distinctive facial features, brachydactyly, hypotonia, and redundant skin folds along the limbs. Most affected infants die of respiratory insufficiency shortly after birth. Both TDI and TDII are caused by heterozygous fibroblast growth factor receptor 3 (FGFR3) missense mutations. Its incidence is 1 in 20 000 to 50 000 births and it is an autosomal dominant condition. The mutation in most TD cases is de novo.

UniProtKB/Swiss-Prot : 73 Thanatophoric dysplasia 1: A neonatal lethal skeletal dysplasia. Affected individuals manifest severe shortening of the limbs with macrocephaly, narrow thorax, short ribs, and curved femurs.

Wikipedia : 74 Thanatophoric dysplasia (thanatophoric dwarfism) is a severe skeletal disorder characterized by a... more...

GeneReviews: NBK1366

Related Diseases for Thanatophoric Dysplasia, Type I

Diseases in the Thanatophoric Dysplasia, Type I family:

Thanatophoric Dysplasia, Type Ii

Diseases related to Thanatophoric Dysplasia, Type I via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 129)
# Related Disease Score Top Affiliating Genes
1 thanatophoric dysplasia, type ii 30.7 STAT1 FGFR3
2 nevus, epidermal 30.5 FGFR3 FGFR2 FGFR1
3 acromesomelic dysplasia, maroteaux type 30.1 NPR2 NPPC FGFR3
4 synostosis 30.1 FGFR3 FGFR2 FGFR1 FGF8
5 brittle bone disorder 30.1 PTH1R FGFR3 COMP COL2A1
6 skeletal dysplasias 29.9 PTH1R NPPC FGFR3 COMP COL2A1
7 multiple epiphyseal dysplasia 29.9 PTH1R FGFR3 COMP COL2A1
8 chromosome 2q35 duplication syndrome 29.9 IHH FGFR3 FGFR2 FGFR1 FGF8
9 achondroplasia, severe, with developmental delay and acanthosis nigricans 29.8 STAT1 PTH1R FGFR4 FGFR3 FGFR2 FGFR1
10 holoprosencephaly 29.7 IHH FGFR3 FGFR2 FGFR1 FGF8
11 acromesomelic dysplasia 29.5 NPR2 NPPC FGFR3 COL2A1
12 achondroplasia 29.1 TK1 PTH1R NPPC FGFR3 FGFR2 FGFR1
13 brachydactyly 28.9 NPR2 IHH FGFR3 FGF9 COMP COL2A1
14 odontochondrodysplasia 28.8 PTH1R NPR2 NPPC IHH FGFR3 FGFR2
15 bone disease 28.5 STAT1 PTH1R FGFR3 FGFR2 FGFR1 FGF9
16 cleft palate, isolated 28.5 IHH FGFR3 FGFR2 FGFR1 FGF8 FGF18
17 craniosynostosis 27.6 IHH FGFR4 FGFR3 FGFR2 FGFR1 FGF9
18 apert syndrome 27.4 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
19 hypochondroplasia 27.2 TK1 NPR2 NPPC IHH FGFR3 FGFR2
20 crouzon syndrome 27.0 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
21 kleeblattschaedel 11.7
22 platyspondylic lethal skeletal dysplasia, torrance type 11.6
23 atelosteogenesis, type i 11.3
24 boomerang dysplasia 11.3
25 hydrocephalus 10.5
26 hemifacial hyperplasia 10.5 FGFR3 FGFR2
27 dwarfism 10.4
28 achondrogenesis 10.4
29 macrocephaly/megalencephaly syndrome, autosomal recessive 10.4
30 polyhydramnios 10.4
31 megalencephaly 10.4
32 testicular spermatocytic seminoma 10.3 FGFR3 FGFR2
33 respiratory failure 10.3
34 fgfr-related craniosynostosis syndromes 10.3 FGFR3 FGFR2 FGFR1
35 encephalocele 10.3
36 plagiocephaly 10.3 FGFR3 FGFR2 FGFR1
37 syndromic craniosynostosis 10.3 FGFR3 FGFR2 FGFR1
38 osteoglophonic dysplasia 10.3 FGFR3 FGFR2 FGFR1
39 hypertelorism, microtia, facial clefting syndrome 10.3 FGFR3 FGFR2 FGFR1
40 jackson-weiss syndrome 10.3 FGFR3 FGFR2 FGFR1
41 achondrogenesis, type ia 10.3
42 schneckenbecken dysplasia 10.3
43 exophthalmos 10.3 FGFR3 FGFR2 FGFR1
44 radioulnar synostosis 10.3 FGFR3 FGFR2 FGFR1
45 osteogenesis imperfecta, type ii 10.3
46 skeletal dysplasia, san diego type 10.3
47 antley-bixler syndrome 10.3 FGFR3 FGFR2 FGFR1
48 luteoma 10.2 FGFR3 FGFR2
49 acanthosis nigricans 10.2
50 keratosis, seborrheic 10.2

Graphical network of the top 20 diseases related to Thanatophoric Dysplasia, Type I:



Diseases related to Thanatophoric Dysplasia, Type I

Symptoms & Phenotypes for Thanatophoric Dysplasia, Type I

Human phenotypes related to Thanatophoric Dysplasia, Type I:

58 31 (show top 50) (show all 64)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000256
2 muscular hypotonia 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001252
3 respiratory insufficiency 58 31 hallmark (90%) Occasional (29-5%),Very frequent (99-80%) HP:0002093
4 skeletal dysplasia 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002652
5 depressed nasal bridge 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0005280
6 brachydactyly 58 31 hallmark (90%) Frequent (79-30%),Very frequent (99-80%) HP:0001156
7 abnormality of the metaphysis 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000944
8 narrow chest 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000774
9 platyspondyly 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000926
10 micromelia 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002983
11 short thorax 58 31 hallmark (90%) Very frequent (99-80%) HP:0010306
12 flat face 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0012368
13 split hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0001171
14 redundant skin 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001582
15 increased nuchal translucency 58 31 frequent (33%) Very frequent (99-80%),Frequent (79-30%) HP:0010880
16 disproportionate short-limb short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0008873
17 pulmonary hypoplasia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002089
18 intellectual disability, profound 58 31 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002187
19 femoral bowing 58 31 hallmark (90%) Very frequent (99-80%) HP:0002980
20 short femur 58 31 hallmark (90%) Very frequent (99-80%) HP:0003097
21 hypoplastic ilia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000946
22 short sacroiliac notch 58 31 hallmark (90%) Very frequent (99-80%) HP:0003185
23 lethal short-limbed short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0008909
24 frontal bossing 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002007
25 kyphosis 58 31 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0002808
26 hearing impairment 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000365
27 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
28 polyhydramnios 58 31 frequent (33%) Occasional (29-5%),Frequent (79-30%) HP:0001561
29 midface retrusion 58 31 frequent (33%) Frequent (79-30%) HP:0011800
30 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0002119
31 proptosis 58 31 frequent (33%) Frequent (79-30%),Frequent (79-30%) HP:0000520
32 aplasia/hypoplasia of the lungs 58 31 frequent (33%) Frequent (79-30%) HP:0006703
33 wide anterior fontanel 58 31 frequent (33%) Frequent (79-30%) HP:0000260
34 excessive wrinkled skin 58 31 frequent (33%) Frequent (79-30%) HP:0007392
35 gray matter heterotopia 31 occasional (7.5%) HP:0002282
36 low-set ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000369
37 seizures 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001250
38 hydrocephalus 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000238
39 hip dysplasia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001385
40 joint stiffness 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001387
41 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
42 acanthosis nigricans 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000956
43 cloverleaf skull 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0002676
44 patent ductus arteriosus 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001643
45 joint hyperflexibility 58 31 occasional (7.5%) Occasional (29-5%) HP:0005692
46 atrial septal defect 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0001631
47 abnormality of the kidney 58 31 occasional (7.5%) Occasional (29-5%),Occasional (29-5%) HP:0000077
48 abnormality of the sacroiliac joint 58 31 occasional (7.5%) Occasional (29-5%),Very frequent (99-80%) HP:0100781
49 bowing of the long bones 58 31 Very frequent (99-80%) HP:0006487
50 global developmental delay 31 HP:0001263

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly
frontal bossing

Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Head And Neck Face:
small face

Skeletal Spine:
severe platyspondyly

Prenatal Manifestations Movement:
decreased fetal activity

Growth Other:
severe growth deficiency in survivors

Skeletal Pelvis:
short and small iliac bones
small sacroiliac notches

Prenatal Manifestations:
prenatal diagnosis by ultrasound

Neurologic Central Nervous System:
hydrocephalus
temporal lobe heterotopias
profound mental retardation and hypotonia in survivors

Chest Ribs Sternum Clavicles And Scapulae:
small abnormally formed scapulae
short ribs
wide-cupped costochondral junctions

Skeletal Skull:
small foramen magnum
cloverleaf skull rarely

Chest External Features:
narrow thorax

Growth Height:
dwarfism, lethal micromelic

Respiratory Lung:
respiratory insufficiency/failure

Skeletal Limbs:
marked shortness and bowing of long bones
'french telephone receiver femurs'
flared and irregular metaphyses

Clinical features from OMIM:

187600

GenomeRNAi Phenotypes related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

26 (show all 11)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased viability GR00055-A-2 9.98 CBL
2 Decreased viability GR00221-A-1 9.98 FGFR1 FGFR3 IHH TK1
3 Decreased viability GR00221-A-2 9.98 CBL FGFR1 FGFR3 IHH TK1
4 Decreased viability GR00221-A-3 9.98 CBL FGFR3
5 Decreased viability GR00221-A-4 9.98 TK1
6 Decreased viability GR00342-S-1 9.98 TK1
7 Decreased viability GR00342-S-2 9.98 TK1
8 Decreased viability GR00342-S-3 9.98 TK1
9 Decreased viability GR00381-A-1 9.98 TK1
10 Decreased viability GR00402-S-2 9.98 CBL FGFR1 FGFR3 TK1
11 Increased human cytomegalovirus (HCMV) strain AD169 replication GR00248-A 9.02 FGFR1 FGFR2 FGFR3 FGFR4 TK1

MGI Mouse Phenotypes related to Thanatophoric Dysplasia, Type I:

45 (show all 22)
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.48 CBL COL2A1 COMP FGF13 FGF2 FGF8
2 homeostasis/metabolism MP:0005376 10.45 CBL COL2A1 COMP FGF1 FGF18 FGF2
3 cardiovascular system MP:0005385 10.44 CBL COL2A1 COMP FGF18 FGF2 FGF8
4 cellular MP:0005384 10.44 CBL COL2A1 COMP FGF13 FGF18 FGF2
5 growth/size/body region MP:0005378 10.43 CBL COL2A1 COMP FGF18 FGF8 FGF9
6 mortality/aging MP:0010768 10.41 CBL COL2A1 FGF13 FGF18 FGF2 FGF8
7 craniofacial MP:0005382 10.36 CBL COL2A1 FGF18 FGF8 FGF9 FGFR1
8 digestive/alimentary MP:0005381 10.35 COL2A1 FGF18 FGF8 FGF9 FGFR1 FGFR2
9 hematopoietic system MP:0005397 10.35 CBL FGF1 FGF2 FGF8 FGF9 FGFR1
10 limbs/digits/tail MP:0005371 10.34 CBL COL2A1 COMP FGF18 FGF8 FGF9
11 endocrine/exocrine gland MP:0005379 10.31 CBL FGF8 FGF9 FGFR1 FGFR2 IHH
12 immune system MP:0005387 10.29 CBL COL2A1 COMP FGF8 FGFR1 FGFR2
13 nervous system MP:0003631 10.22 COL2A1 FGF1 FGF13 FGF2 FGF8 FGFR1
14 muscle MP:0005369 10.16 CBL COMP FGF2 FGF8 FGF9 FGFR1
15 hearing/vestibular/ear MP:0005377 10.15 CBL COL2A1 FGF2 FGF8 FGF9 FGFR1
16 normal MP:0002873 10.07 COL2A1 COMP FGF1 FGF8 FGF9 FGFR1
17 reproductive system MP:0005389 10 CBL FGF2 FGF8 FGF9 FGFR1 FGFR2
18 respiratory system MP:0005388 9.93 CBL COL2A1 FGF18 FGF8 FGF9 FGFR2
19 neoplasm MP:0002006 9.91 FGF2 FGFR2 FGFR3 FGFR4 PTH1R STAT1
20 renal/urinary system MP:0005367 9.87 COL2A1 FGF8 FGF9 FGFR1 FGFR2 FGFR3
21 skeleton MP:0005390 9.86 CBL COL2A1 COMP FGF18 FGF2 FGF8
22 vision/eye MP:0005391 9.32 COL2A1 FGF2 FGF8 FGF9 FGFR1 FGFR2

Drugs & Therapeutics for Thanatophoric Dysplasia, Type I

Search Clinical Trials , NIH Clinical Center for Thanatophoric Dysplasia, Type I

Cochrane evidence based reviews: thanatophoric dysplasia

Genetic Tests for Thanatophoric Dysplasia, Type I

Genetic tests related to Thanatophoric Dysplasia, Type I:

# Genetic test Affiliating Genes
1 Thanatophoric Dysplasia Type 1 29 FGFR3

Anatomical Context for Thanatophoric Dysplasia, Type I

MalaCards organs/tissues related to Thanatophoric Dysplasia, Type I:

40
Bone, Skin, Lung, Eye, Heart, Temporal Lobe, Brain

Publications for Thanatophoric Dysplasia, Type I

Articles related to Thanatophoric Dysplasia, Type I:

(show top 50) (show all 438)
# Title Authors PMID Year
1
Thanatophoric dysplasia caused by double missense FGFR3 mutations. 54 61 24 56 6
19449430 2009
2
Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia. 54 61 24 56 6
9677066 1998
3
Another mutation that results in the substitution of an unpaired cysteine residue in the extracellular domain of FGFR3 in thanatophoric dysplasia type I. 54 61 56 6
8589699 1995
4
Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3. 54 61 56 6
7773297 1995
5
Somatic and germline mosaicism for a R248C missense mutation in FGFR3, resulting in a skeletal dysplasia distinct from thanatophoric dysplasia. 54 61 24 6
12833394 2003
6
The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum. 54 61 24 6
12624096 2003
7
A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene. 54 61 24 6
10053006 1999
8
Prenatal diagnosis of thanatophoric dysplasia by mutational analysis of the fibroblast growth factor receptor 3 gene and a proposed correction of previously published PCR results. 61 56 6
10073901 1999
9
Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1). 54 56 6
8845844 1996
10
Platyspondylic lethal skeletal dysplasia, San Diego type, is caused by FGFR3 mutations. 61 24 56
10360402 1999
11
Growth and development in thanatophoric dysplasia. 61 24 56
2596513 1989
12
Activating mutations in FGFR3 and HRAS reveal a shared genetic origin for congenital disorders and testicular tumors. 54 61 6
19855393 2009
13
Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. 54 61 6
16841094 2006
14
Thanatophoric dysplasia type I with syndactyly. 54 61 6
9843049 1998
15
Abnormal FGFR 3 expression in cartilage of thanatophoric dysplasia fetuses. 54 61 56
9302269 1997
16
The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. 61 56
18698630 2008
17
Thanatophoric dysplasia type 2 with encephalocele during the second trimester. 61 6
16752380 2006
18
The cytoplasmic tyrosine kinase Pyk2 as a novel effector of fibroblast growth factor receptor 3 activation. 54 61 24
15105428 2004
19
Thanatophoric Dysplasia 61 6
20301540 2004
20
Overexpression of FGFR3, Stat1, Stat5 and p21Cip1 correlates with phenotypic severity and defective chondrocyte differentiation in FGFR3-related chondrodysplasias. 54 61 24
14751560 2004
21
Occurrence of thanatophoric dysplasia type I (R248C) and hypochondroplasia (N540K) mutations in two patients with achondroplasia phenotype. 54 61 24
11754059 2001
22
Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. 54 61 24
10377013 1999
23
Fibroblast growth factor receptor 3 mutations promote apoptosis but do not alter chondrocyte proliferation in thanatophoric dysplasia. 54 61 24
9582336 1998
24
Lys650Met substitution in the tyrosine kinase domain of the fibroblast growth factor receptor gene causes thanatophoric dysplasia Type I. Mutations in brief no. 199. Online. 61 6
10671061 1998
25
Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is associated with increased expression and activating mutations of fibroblast growth factor receptor 3. 54 6
9207791 1997
26
Long-term survival in typical thanatophoric dysplasia type 1. 61 56
9182787 1997
27
Japanese cases of type 1 thanatophoric dysplasia exclusively carry a C to T transition at nucleotide 742 of the fibroblast growth factor receptor 3 gene. 61 6
8858131 1996
28
Antenatal sonographic diagnosis of thanatophoric dysplasia: a report of three cases and a review of the literature with special emphasis on the differential diagnosis. 61 56
8843623 1996
29
Stop codon FGFR3 mutations in thanatophoric dwarfism type 1. 54 6
7647778 1995
30
De novo 1;10 balanced translocation in an infant with thanatophoric dysplasia: a clue to the locus of the candidate gene. 61 56
7643360 1995
31
Thanatophoric dysplasia of the straight-bone type (type 2). 61 56
1345514 1992
32
Thanatophoric dysplasia in monozygotic twins discordant for cloverleaf skull: prenatal diagnosis, clinical and pathological findings. 61 56
1308351 1992
33
Thanatophoric dysplasia in identical twins. 61 56
2585471 1989
34
Thanatophoric dysplasia in identical twins. 61 56
2716037 1989
35
Prevalence of lethal osteochondrodysplasias in Denmark. 61 56
2789000 1989
36
Thanatophoric dysplasia: an autosomal dominant condition? 61 56
3239573 1988
37
Abnormal ossification in thanatophoric dysplasia. 61 56
3132190 1988
38
A boy with thanatophoric dysplasia surviving 212 days. 61 56
3436092 1987
39
The birth prevalence rates for the skeletal dysplasias. 61 56
3746832 1986
40
Thanatophoric dysplasia: fetal manifestations and prenatal diagnosis. 61 56
4073120 1985
41
Lethal neonatal chondrodysplasias in the West of Scotland 1970-1983 with a description of a thanatophoric, dysplasialike, autosomal recessive disorder, Glasgow variant. 61 56
3901754 1985
42
Prenatal diagnosis of thanatophoric dysplasia at 24 weeks. 61 56
6741994 1984
43
Thanatophoric dysplasia of identical twins. 61 56
6538757 1984
44
Neuropathologic findings in thanatophoric dysplasia. 61 56
6464678 1984
45
Neuropathological findings in thanatophoric dysplasia. 61 56
6687528 1983
46
Further heterogeneity within lethal neonatal short-limbed dwarfism: the platyspondylic types. 61 56
448481 1979
47
Molecular Analysis of a Case of Thanatophoric Dysplasia Reveals Two de novo FGFR3 Missense Mutations located in cis. 61 24
23573386 2013
48
Clinical epidemiology of skeletal dysplasias in South America. 61 24
22407836 2012
49
Atypical achondroplasia due to somatic mosaicism for the common thanatophoric dysplasia mutation R248C. 61 24
22106050 2012
50
Early prenatal diagnosis of skeletal anomalies. 61 24
21210484 2011

Variations for Thanatophoric Dysplasia, Type I

ClinVar genetic disease variations for Thanatophoric Dysplasia, Type I:

6 (show all 24) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FGFR3 NM_000142.4(FGFR3):c.1111A>T (p.Ser371Cys)SNV Pathogenic 16333 rs121913484 4:1806092-1806092 4:1804365-1804365
2 FGFR3 NM_000142.4(FGFR3):c.2419T>G (p.Ter807Gly)SNV Pathogenic 16334 rs121913101 4:1808987-1808987 4:1807260-1807260
3 FGFR3 NM_000142.4(FGFR3):c.1620C>G (p.Asn540Lys)SNV Pathogenic 16338 rs28933068 4:1807371-1807371 4:1805644-1805644
4 FGFR3 NM_000142.4(FGFR3):c.746C>G (p.Ser249Cys)SNV Pathogenic 16339 rs121913483 4:1803568-1803568 4:1801841-1801841
5 FGFR3 NM_000142.4(FGFR3):c.749C>G (p.Pro250Arg)SNV Pathogenic 16340 rs4647924 4:1803571-1803571 4:1801844-1801844
6 FGFR3 NM_000142.4(FGFR3):c.251C>T (p.Ser84Leu)SNV Pathogenic 16358 rs121913116 4:1801122-1801122 4:1799395-1799395
7 FGFR3 NM_000142.4(FGFR3):c.1108G>T (p.Gly370Cys)SNV Pathogenic 16359 rs121913479 4:1806089-1806089 4:1804362-1804362
8 FGFR3 NM_000142.4(FGFR3):c.2419T>C (p.Ter807Arg)SNV Pathogenic 65561 rs121913101 4:1808987-1808987 4:1807260-1807260
9 FGFR3 NM_000142.4(FGFR3):c.2420G>T (p.Ter807Leu)SNV Pathogenic 65562 rs397515514 4:1808988-1808988 4:1807261-1807261
10 FGFR3 NM_000142.4(FGFR3):c.2421A>C (p.Ter807Cys)SNV Pathogenic 65563 rs121913103 4:1808989-1808989 4:1807262-1807262
11 FGFR3 NM_000142.4(FGFR3):c.2421A>G (p.Ter807Trp)SNV Pathogenic 65564 rs121913103 4:1808989-1808989 4:1807262-1807262
12 FGFR3 NM_000142.4(FGFR3):c.1949A>C (p.Lys650Thr)SNV Pathogenic 65855 rs121913105 4:1807890-1807890 4:1806163-1806163
13 FGFR3 NM_000142.4(FGFR3):c.2419T>A (p.Ter807Arg)SNV Pathogenic 16335 rs121913101 4:1808987-1808987 4:1807260-1807260
14 FGFR3 NM_000142.4(FGFR3):c.2421A>T (p.Ter807Cys)SNV Pathogenic 16336 rs121913103 4:1808989-1808989 4:1807262-1807262
15 FGFR3 NM_000142.4(FGFR3):c.1620C>A (p.Asn540Lys)SNV Pathogenic 16337 rs28933068 4:1807371-1807371 4:1805644-1805644
16 FGFR3 NM_000142.4(FGFR3):c.742C>T (p.Arg248Cys)SNV Pathogenic 16332 rs121913482 4:1803564-1803564 4:1801837-1801837
17 FGFR3 NM_000142.4(FGFR3):c.1949A>T (p.Lys650Met)SNV Pathogenic 16341 rs121913105 4:1807890-1807890 4:1806163-1806163
18 FGFR3 NM_000142.4(FGFR3):c.1118A>G (p.Tyr373Cys)SNV Conflicting interpretations of pathogenicity 16342 rs121913485 4:1806099-1806099 4:1804372-1804372
19 FGFR3 NM_001163213.1(FGFR3):c.1144G>A (p.Gly382Arg)SNV Conflicting interpretations of pathogenicity 16327 rs28931614 4:1806119-1806119 4:1804392-1804392
20 FGFR3 NM_000142.4(FGFR3):c.1993G>T (p.Ala665Ser)SNV Uncertain significance 465350 rs764892330 4:1808017-1808017 4:1806290-1806290
21 FGFR3 NM_000142.4(FGFR3):c.2153A>G (p.Asn718Ser)SNV Uncertain significance 521225 rs139773438 4:1808395-1808395 4:1806668-1806668
22 FGFR3 NM_000142.4(FGFR3):c.200G>A (p.Gly67Asp)SNV Uncertain significance 546226 rs369232922 4:1801071-1801071 4:1799344-1799344
23 FGFR3 NM_000142.4(FGFR3):c.1519G>A (p.Val507Met)SNV Uncertain significance 633464 rs1560437651 4:1807188-1807188 4:1805461-1805461
24 FGFR3 NM_000142.4(FGFR3):c.1454A>G (p.Gln485Arg)SNV no interpretation for the single variant 446197 rs267606808 4:1807123-1807123 4:1805396-1805396

UniProtKB/Swiss-Prot genetic disease variations for Thanatophoric Dysplasia, Type I:

73
# Symbol AA change Variation ID SNP ID
1 FGFR3 p.Arg248Cys VAR_004148 rs121913482
2 FGFR3 p.Ser249Cys VAR_004149 rs121913483
3 FGFR3 p.Gly370Cys VAR_004151 rs121913479
4 FGFR3 p.Ser371Cys VAR_004152 rs121913484
5 FGFR3 p.Tyr373Cys VAR_004153 rs121913485
6 FGFR3 p.Lys650Met VAR_004161 rs121913105

Expression for Thanatophoric Dysplasia, Type I

Search GEO for disease gene expression data for Thanatophoric Dysplasia, Type I.

Pathways for Thanatophoric Dysplasia, Type I

Pathways related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

(show top 50) (show all 59)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.21 STAT1 PTH1R IHH FGFR4 FGFR3 FGFR2
2
Show member pathways
14.05 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF9
3
Show member pathways
13.94 STAT1 IHH FGFR4 FGFR3 FGFR2 FGFR1
4
Show member pathways
13.85 FGFR4 FGFR3 FGFR2 FGFR1 FGF8 FGF2
5
Show member pathways
13.82 STAT1 IHH FGFR4 FGFR3 FGFR2 FGFR1
6
Show member pathways
13.8 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF9
7
Show member pathways
13.67 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF9
8
Show member pathways
13.65 IHH FGFR4 FGFR3 FGFR2 FGFR1 FGF8
9
Show member pathways
13.57 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
10
Show member pathways
13.56 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
11
Show member pathways
13.52 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF8
12
Show member pathways
13.5 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF9
13
Show member pathways
13.45 NPR2 FGFR4 FGFR3 FGFR2 FGFR1 FGF8
14
Show member pathways
13.42 NPR2 FGFR4 FGFR3 FGFR2 FGFR1 FGF8
15
Show member pathways
13.41 FGFR4 FGFR3 FGFR2 FGFR1 FGF8 FGF2
16
Show member pathways
13.25 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
17
Show member pathways
13.21 FGFR4 FGFR3 FGFR2 FGFR1 FGF8 FGF2
18
Show member pathways
13.19 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF8
19
Show member pathways
13.03 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
20
Show member pathways
12.98 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF9
21 12.94 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF9
22 12.93 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
23
Show member pathways
12.9 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
24
Show member pathways
12.89 FGFR2 FGFR1 FGF9 FGF8 FGF2 FGF18
25
Show member pathways
12.86 FGFR4 FGFR3 FGFR2 FGFR1 FGF8 FGF2
26
Show member pathways
12.86 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
27
Show member pathways
12.84 FGFR2 FGFR1 FGF9 FGF8 FGF2 FGF18
28 12.76 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
29
Show member pathways
12.66 STAT1 FGFR3 FGFR2 FGF2 CBL
30
Show member pathways
12.65 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
31
Show member pathways
12.56 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
32
Show member pathways
12.53 FGFR4 FGFR3 FGFR2 FGFR1 FGF8 FGF2
33
Show member pathways
12.49 FGFR4 FGFR3 FGFR2 FGFR1
34
Show member pathways
12.44 FGFR4 FGFR3 FGFR2 FGFR1
35 12.41 FGFR4 FGFR3 FGFR2 CBL
36
Show member pathways
12.4 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
37
Show member pathways
12.37 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF8
38
Show member pathways
12.35 FGFR4 FGFR3 FGFR2 FGFR1 FGF2
39
Show member pathways
12.32 STAT1 FGFR1 FGF2 CBL
40 12.32 IHH FGFR1 FGF2 CBL
41 12.31 FGFR4 FGFR3 FGFR2 FGFR1 FGF2 FGF1
42 12.24 FGFR4 FGFR3 FGFR2 FGFR1 FGF2
43
Show member pathways
12.21 FGFR4 FGFR3 FGFR2 FGFR1
44 12.13 FGFR3 FGFR2 FGFR1 FGF8 FGF2 COL2A1
45
Show member pathways
12.06 STAT1 FGFR1 FGF9 FGF8 FGF2 FGF1
46
Show member pathways
12.05 STAT1 FGFR4 FGFR3 FGFR2 FGFR1 FGF9
47 12.04 FGFR4 FGFR3 FGFR2 FGFR1 FGF2 FGF1
48 11.96 FGFR4 FGFR3 FGFR1 FGF8 FGF2
49
Show member pathways
11.94 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
50
Show member pathways
11.82 FGFR3 FGF9 FGF8 FGF2 FGF18 FGF1

GO Terms for Thanatophoric Dysplasia, Type I

Cellular components related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.76 NPPC IHH FGF9 FGF2 FGF18 FGF1
2 extracellular matrix GO:0031012 9.56 IHH FGF1 COMP COL2A1
3 extracellular region GO:0005576 9.47 NPPC IHH FGFR4 FGFR3 FGFR2 FGFR1
4 receptor complex GO:0043235 9.35 PTH1R FGFR4 FGFR3 FGFR2 FGFR1

Biological processes related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

(show top 50) (show all 60)
# Name GO ID Score Top Affiliating Genes
1 signal transduction GO:0007165 10.34 STAT1 PTH1R NPR2 FGF9 FGF2 FGF18
2 protein phosphorylation GO:0006468 10.13 NPR2 FGFR4 FGFR3 FGFR2 FGFR1
3 angiogenesis GO:0001525 10.02 FGFR2 FGFR1 FGF9 FGF2 FGF18 FGF1
4 regulation of gene expression GO:0010468 10.01 IHH FGFR1 COMP COL2A1
5 cell-cell signaling GO:0007267 10.01 IHH FGFR3 FGFR2 FGF9 FGF18 FGF13
6 in utero embryonic development GO:0001701 10 PTH1R IHH FGFR2 FGFR1
7 positive regulation of ERK1 and ERK2 cascade GO:0070374 10 FGFR4 FGFR3 FGFR2 FGF8 FGF2 FGF18
8 protein autophosphorylation GO:0046777 9.99 FGFR4 FGFR3 FGFR2 FGFR1
9 peptidyl-tyrosine phosphorylation GO:0018108 9.97 FGFR4 FGFR3 FGFR2 FGFR1
10 skeletal system development GO:0001501 9.97 PTH1R IHH FGFR3 FGFR1 COMP COL2A1
11 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.95 FGFR4 FGFR3 FGFR2 FGFR1
12 positive regulation of MAPK cascade GO:0043410 9.94 FGFR3 FGFR2 FGFR1 FGF9
13 positive regulation of epithelial cell proliferation GO:0050679 9.93 IHH FGFR2 FGF9 FGF1
14 positive regulation of MAP kinase activity GO:0043406 9.92 FGFR1 FGF2 FGF18 FGF1
15 bone development GO:0060348 9.92 NPR2 FGFR2 FGF8 COL2A1
16 positive regulation of protein kinase B signaling GO:0051897 9.91 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
17 response to ethanol GO:0045471 9.9 NPPC FGFR2 CBL
18 cartilage development GO:0051216 9.88 IHH COMP COL2A1
19 bone mineralization GO:0030282 9.88 PTH1R FGFR3 FGFR2 COMP
20 inner ear morphogenesis GO:0042472 9.88 FGFR2 FGFR1 FGF9 FGF8 COL2A1
21 lung development GO:0030324 9.88 FGFR2 FGFR1 FGF9 FGF8 FGF18 FGF1
22 ossification GO:0001503 9.87 PTH1R NPR2 NPPC IHH FGF18 COMP
23 positive regulation of blood vessel endothelial cell migration GO:0043536 9.86 FGFR1 FGF2 FGF18
24 positive regulation of cardiac muscle cell proliferation GO:0060045 9.86 FGFR2 FGFR1 FGF9 FGF2
25 skeletal system morphogenesis GO:0048705 9.85 FGFR2 FGFR1 COL2A1
26 positive regulation of cell division GO:0051781 9.85 FGFR2 FGF9 FGF8 FGF2 FGF1
27 MAPK cascade GO:0000165 9.85 FGFR4 FGFR3 FGFR2 FGFR1 FGF9 FGF8
28 cell maturation GO:0048469 9.84 PTH1R IHH FGFR1
29 bone morphogenesis GO:0060349 9.84 FGFR3 FGFR2 COMP
30 chondrocyte differentiation GO:0002062 9.83 PTH1R FGFR3 FGFR1 FGF9 COL2A1
31 endochondral ossification GO:0001958 9.81 FGFR3 FGF18 COL2A1
32 branching involved in salivary gland morphogenesis GO:0060445 9.79 FGFR2 FGFR1 FGF8
33 chondrocyte proliferation GO:0035988 9.78 IHH FGFR3 COMP
34 organ induction GO:0001759 9.77 FGFR1 FGF8 FGF1
35 positive regulation of phospholipase activity GO:0010518 9.77 FGFR3 FGFR2 FGFR1
36 positive regulation of mesenchymal cell proliferation GO:0002053 9.77 STAT1 IHH FGFR2 FGFR1 FGF9
37 endochondral bone growth GO:0003416 9.76 FGFR3 FGFR2 COMP
38 lung-associated mesenchyme development GO:0060484 9.74 FGFR2 FGFR1 FGF9
39 positive regulation of cell proliferation GO:0008284 9.73 STAT1 PTH1R IHH FGFR4 FGFR3 FGFR2
40 embryonic digestive tract morphogenesis GO:0048557 9.72 IHH FGFR2
41 interleukin-6-mediated signaling pathway GO:0070102 9.72 STAT1 CBL
42 positive regulation of DNA biosynthetic process GO:2000573 9.72 FGFR4 FGF2
43 generation of neurons GO:0048699 9.72 FGFR1 FGF8
44 positive regulation of phospholipase C activity GO:0010863 9.72 FGFR1 FGF2
45 limb bud formation GO:0060174 9.71 FGFR2 COL2A1
46 cGMP biosynthetic process GO:0006182 9.71 NPR2 NPPC
47 mesenchymal cell differentiation GO:0048762 9.71 FGFR2 FGFR1
48 reproductive process GO:0022414 9.7 NPR2 NPPC
49 receptor guanylyl cyclase signaling pathway GO:0007168 9.7 NPR2 NPPC
50 proteoglycan metabolic process GO:0006029 9.7 IHH COL2A1

Molecular functions related to Thanatophoric Dysplasia, Type I according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein kinase activity GO:0004672 9.85 NPR2 FGFR4 FGFR3 FGFR2 FGFR1
2 growth factor activity GO:0008083 9.73 FGF9 FGF8 FGF2 FGF18 FGF13 FGF1
3 protein tyrosine kinase activity GO:0004713 9.71 FGFR4 FGFR3 FGFR2 FGFR1
4 heparin binding GO:0008201 9.7 FGFR4 FGFR2 FGFR1 FGF9 FGF2 FGF1
5 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.67 FGFR4 FGFR3 FGFR2 FGFR1
6 fibroblast growth factor binding GO:0017134 9.62 FGFR4 FGFR3 FGFR2 FGFR1
7 proteoglycan binding GO:0043394 9.48 COMP COL2A1
8 receptor-receptor interaction GO:0090722 9.43 FGFR1 FGF2
9 fibroblast growth factor receptor binding GO:0005104 9.35 FGF9 FGF8 FGF2 FGF18 FGF1
10 fibroblast growth factor-activated receptor activity GO:0005007 8.92 FGFR4 FGFR3 FGFR2 FGFR1

Sources for Thanatophoric Dysplasia, Type I

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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