SADDAN
MCID: ACH043
MIFTS: 62

Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans (SADDAN)

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

Aliases & Classifications for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

MalaCards integrated aliases for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

Name: Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans 57 25 74 72
Saddan 57 12 75 53 25 59 74 37 15 40
Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans 12 53 25 29 6
Saddan Dysplasia 57 12 53 25 74
Severe Achondroplasia-Developmental Delay-Acanthosis Nigricans Syndrome 53 59
Ssb Syndrome 53 25
Skeleton Skin Brain Syndrome 53
Skeleton-Skin-Brain Syndrome 25
Achondroplasia 44

Characteristics:

Orphanet epidemiological data:

59
severe achondroplasia-developmental delay-acanthosis nigricans syndrome
Inheritance: Autosomal dominant,Not applicable; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
clinical overlap with thanatophoric dysplasia i () and severe achondroplasia ()


HPO:

32
achondroplasia, severe, with developmental delay and acanthosis nigricans:
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0111158
OMIM 57 616482
KEGG 37 H02069
MeSH 44 D000130
ICD10 via Orphanet 34 Q77.4
UMLS via Orphanet 73 C2674173
Orphanet 59 ORPHA85165
MedGen 42 CN231689
UMLS 72 C2674173

Summaries for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Genetics Home Reference : 25 SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare disorder of bone growth characterized by skeletal, brain, and skin abnormalities. All people with this condition have extremely short stature with particularly short arms and legs. Other features include unusual bowing of the leg bones; a small chest with short ribs and curved collar bones; short, broad fingers; and folds of extra skin on the arms and legs. Structural abnormalities of the brain cause seizures, profound developmental delay, and intellectual disability. Several affected individuals also have had episodes in which their breathing slows or stops for short periods (apnea). Acanthosis nigricans, a progressive skin disorder characterized by thick, dark, velvety skin, is another characteristic feature of SADDAN that develops in infancy or early childhood.

MalaCards based summary : Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans, also known as saddan, is related to achondroplasia and hypochondroplasia, and has symptoms including seizures An important gene associated with Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans is FGFR3 (Fibroblast Growth Factor Receptor 3), and among its related pathways/superpathways are MAPK signaling pathway and Ras signaling pathway. The drugs Simvastatin and Lipid Regulating Agents have been mentioned in the context of this disorder. Affiliated tissues include skin, brain and bone, and related phenotypes are brain atrophy and intellectual disability, severe

Disease Ontology : 12 An autosomal dominant disease characterized by severe achondroplasia, developmental delay and acanthosis nigricans that has material basis in heterozygous mutation in the FGFR3 gene on chromosome 4p16.

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 85165DefinitionSevere achondroplasia-developmental delay-acanthosis nigricans syndrome is characterised by the association of severe achondroplasia with developmental delay and acanthosis nigricans. It has been described in four unrelated individuals. Structural central nervous system anomalies, seizures and hearing loss were also reported, together with bowing of the clavicle, femur, tibia and fibula in some cases. The syndrome is caused by a Lys650Met substitution in the kinase domain of fibroblast growth factor receptor 3 (encoded by the FGFR3 gene; 4p16.3).Visit the Orphanet disease page for more resources.

KEGG : 37
SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3 (FGFR3).

UniProtKB/Swiss-Prot : 74 Achondroplasia, severe, with developmental delay and acanthosis nigricans: A severe form of achondroplasia associated with developmental delay and acanthosis nigricans. Patients manifest short-limb dwarfism, with a long, narrow trunk, short extremities, particularly in the proximal (rhizomelic) segments, a large head with frontal bossing, hypoplasia of the midface and a trident configuration of the hands. Acanthosis nigricans is a skin condition characterized by brown-pigmented, velvety verrucosities in body folds and creases.

Wikipedia : 75 Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), is a very rare genetic... more...

More information from OMIM: 616482

Related Diseases for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Diseases related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 280)
# Related Disease Score Top Affiliating Genes
1 achondroplasia 35.2 FGFR3 FGFR2 FGFR1
2 hypochondroplasia 33.5 FGFR3 FGFR2 FGFR1
3 synostosis 30.6 FGFR3 FGFR2 FGFR1
4 thanatophoric dysplasia, type i 30.6 STAT1 FGFR3 FGFR2 FGFR1 FGF13
5 thanatophoric dysplasia, type ii 30.6 STAT1 FGFR3
6 plagiocephaly 30.3 FGFR3 FGFR2 FGFR1
7 crouzon syndrome 30.1 FGFR3 FGFR2 FGFR1 FGF13
8 bone disease 30.0 SRC PTHLH FGFR3 FGFR2
9 pfeiffer syndrome 29.7 FGFR3 FGFR2 FGFR1
10 short-limb skeletal dysplasia with severe combined immunodeficiency 12.2
11 dwarfism 11.8
12 hydrocephalus, congenital, 1 11.5
13 pseudoachondroplasia 11.5
14 mesomelia 11.5
15 atelosteogenesis, type i 11.2
16 boomerang dysplasia 11.2
17 hemifacial hyperplasia 10.6 FGFR3 FGFR2
18 hydrocephalus 10.6
19 congenital hydrocephalus 10.6
20 spinal stenosis 10.6
21 skeletal dysplasias 10.5
22 sleep apnea 10.5
23 acanthosis nigricans 10.3
24 osteoglophonic dysplasia 10.3 FGFR3 FGFR2 FGFR1
25 jackson-weiss syndrome 10.3 FGFR3 FGFR2 FGFR1
26 craniosynostosis 10.3
27 hypotonia 10.3
28 radioulnar synostosis 10.3 FGFR3 FGFR2 FGFR1
29 nevus, epidermal 10.2
30 down syndrome 10.2
31 otitis media 10.2
32 overgrowth syndrome 10.2
33 apert syndrome 10.2 FGFR3 FGFR2 FGFR1
34 bone development disease 10.2 FGFR3 FGFR2 FGFR1
35 lacrimoauriculodentodigital syndrome 10.2 FGFR3 FGFR2 FGFR1
36 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
37 spondyloepiphyseal dysplasia with congenital joint dislocations 10.1
38 spondyloepiphyseal dysplasia congenita 10.1
39 respiratory failure 10.1
40 lung disease 10.1
41 back pain 10.1
42 skeletal dysplasia, san diego type 10.1
43 saethre-chotzen syndrome 10.1 FGFR3 FGFR2 FGFR1
44 luteoma 10.1 FGFR3 FGFR2
45 motion sickness 10.1
46 odontochondrodysplasia 10.1
47 syringomyelia, noncommunicating isolated 10.1
48 macrocephaly/megalencephaly syndrome, autosomal recessive 10.1
49 pulmonary hypertension 10.1
50 scoliosis 10.1

Graphical network of the top 20 diseases related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:



Diseases related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans

Symptoms & Phenotypes for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Human phenotypes related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

59 32 (show all 39)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 brain atrophy 59 32 hallmark (90%) Very frequent (99-80%) HP:0012444
2 intellectual disability, severe 59 32 hallmark (90%) Very frequent (99-80%) HP:0010864
3 acanthosis nigricans 59 32 hallmark (90%) Very frequent (99-80%) HP:0000956
4 severe global developmental delay 59 32 hallmark (90%) Very frequent (99-80%) HP:0011344
5 aplasia/hypoplasia of the mandible 59 32 hallmark (90%) Very frequent (99-80%) HP:0009118
6 metaphyseal chondrodysplasia 59 32 hallmark (90%) Very frequent (99-80%) HP:0005871
7 generalized-onset seizure 59 32 hallmark (90%) Very frequent (99-80%) HP:0002197
8 hypoplasia of the corpus callosum 59 32 hallmark (90%) Very frequent (99-80%) HP:0002079
9 enlarged cerebellum 59 32 hallmark (90%) Very frequent (99-80%) HP:0012081
10 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
11 abnormality of the clavicle 59 32 frequent (33%) Frequent (79-30%) HP:0000889
12 femoral bowing 59 32 frequent (33%) Frequent (79-30%) HP:0002980
13 tibial bowing 59 32 frequent (33%) Frequent (79-30%) HP:0002982
14 fibular bowing 59 32 frequent (33%) Frequent (79-30%) HP:0010502
15 gastroesophageal reflux 32 occasional (7.5%) HP:0002020
16 pulmonary arterial hypertension 32 occasional (7.5%) HP:0002092
17 congestive heart failure 32 occasional (7.5%) HP:0001635
18 high myopia 32 occasional (7.5%) HP:0011003
19 exotropia 32 occasional (7.5%) HP:0000577
20 frontal bossing 32 HP:0002007
21 hydrocephalus 32 HP:0000238
22 intellectual disability 32 HP:0001249
23 seizures 32 HP:0001250
24 megalencephaly 32 HP:0001355
25 kyphosis 32 HP:0002808
26 sleep apnea 32 HP:0010535
27 hearing impairment 32 HP:0000365
28 global developmental delay 32 HP:0001263
29 depressed nasal bridge 32 HP:0005280
30 platyspondyly 32 HP:0000926
31 rhizomelia 32 HP:0008905
32 otitis media 32 HP:0000388
33 severe short stature 32 HP:0003510
34 redundant skin 32 HP:0001582
35 midface retrusion 32 HP:0011800
36 wide anterior fontanel 32 HP:0000260
37 lumbar hyperlordosis 32 HP:0002938
38 mesomelia 32 HP:0003027
39 central apnea 32 HP:0002871

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Face:
frontal bossing
midface hypoplasia

Head And Neck Head:
megalencephaly
large anterior fontanel

Respiratory:
sleep apnea
respiratory compromise at birth

Skin Nails Hair Skin:
acanthosis nigricans
redundant skin folds on upper and lower limbs

Head And Neck Ears:
otitis media
hearing loss, mild-to-moderate

Head And Neck Eyes:
exotropia (in some patients)
high myopia (in some patients)

Cardiovascular Vascular:
pulmonary hypertension (in some patients)

Chest External Features:
small chest with flaring costal margins

Skeletal Pelvis:
posterior rotation of hips

Neurologic Central Nervous System:
hydrocephalus
seizures
central apnea
developmental delay
thin corpus callosum
more
Skeletal Spine:
kyphosis
platyspondyly
lumbar lordosis
cervical spinal stenosis

Head And Neck Nose:
depressed nasal bridge

Skeletal Limbs:
rhizomelia
mesomelia
anterior bowing of femora
posterior bowing of tibiae

Growth Height:
dwarfism
short stature, severe disproportionate

Abdomen Gastrointestinal:
gastroesophageal reflux (in some patients)

Cardiovascular Heart:
congestive heart failure (in some patients)

Skeletal Skull:
overgrowth of mandible in adults
pneumatization of the sinuses

Clinical features from OMIM:

616482

UMLS symptoms related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:


seizures

GenomeRNAi Phenotypes related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased substrate adherent cell growth GR00193-A-1 9.91 MAPK3
2 Decreased substrate adherent cell growth GR00193-A-2 9.91 FGFR2 MAPK3 PTK2B
3 Decreased substrate adherent cell growth GR00193-A-3 9.91 FGFR2 FGFR3 MAPK3 PTK2B
4 Decreased substrate adherent cell growth GR00193-A-4 9.91 PTK2B
5 Decreased cell migration GR00055-A-1 9.8 FGFR3 JAK1 MAPK3 PLCG1 PTK2B PXN
6 Decreased telomerase activity GR00156-A 9.33 FGFR3 MAPK3 SRC
7 Decreased viability in HMC1.1 cells GR00105-A-0 9.26 JAK1 PTK2 PTK2B SRC
8 Decreased viability with paclitaxel GR00179-A-1 8.92 MAPK3 PTK2 SRC
9 Decreased viability with paclitaxel GR00179-A-3 8.92 MAPK3

MGI Mouse Phenotypes related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

46 (show all 23)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.53 FGF13 FGFR1 FGFR2 FGFR3 FOXM1 FRS2
2 cardiovascular system MP:0005385 10.48 FGFR1 FGFR2 FOXM1 FRS2 HPSE JAK1
3 growth/size/body region MP:0005378 10.4 FGFR1 FGFR2 FGFR3 FRS2 JAK1 MAPK3
4 immune system MP:0005387 10.36 FGFR1 FGFR2 FGFR3 FOXM1 HPSE JAK1
5 behavior/neurological MP:0005386 10.35 CLSTN2 FGF13 FGFR1 FGFR2 FGFR3 JAK1
6 endocrine/exocrine gland MP:0005379 10.35 FGFR1 FGFR2 FOXM1 HPSE JAK1 MAPK3
7 hematopoietic system MP:0005397 10.35 FGF1 FGFR1 FGFR2 FGFR3 HPSE JAK1
8 mortality/aging MP:0010768 10.34 FGF13 FGFR1 FGFR2 FGFR3 FOXM1 FRS2
9 digestive/alimentary MP:0005381 10.32 FGFR1 FGFR2 FGFR3 FOXM1 MAPK3 PLCG1
10 homeostasis/metabolism MP:0005376 10.3 FGF1 FGFR1 FGFR2 FGFR3 FOXM1 JAK1
11 craniofacial MP:0005382 10.29 FGFR1 FGFR2 FGFR3 FRS2 JAK1 MAPK3
12 embryo MP:0005380 10.27 FGFR1 FGFR2 FRS2 MAPK3 PLCG1 PTK2
13 integument MP:0010771 10.27 FGFR1 FGFR2 FGFR3 HPSE JAK1 MAPK3
14 nervous system MP:0003631 10.21 CLSTN2 FGF1 FGF13 FGFR1 FGFR2 FGFR3
15 limbs/digits/tail MP:0005371 10.18 FGFR1 FGFR2 FGFR3 FRS2 JAK1 PTHLH
16 hearing/vestibular/ear MP:0005377 10.15 FGFR1 FGFR2 FGFR3 FRS2 JAK1 MAPK3
17 neoplasm MP:0002006 10.06 FGFR2 FGFR3 FOXM1 MAPK3 PTHLH PTK2
18 normal MP:0002873 10.02 FGF1 FGFR1 FGFR2 FGFR3 JAK1 PTHLH
19 liver/biliary system MP:0005370 10 FGFR2 FOXM1 JAK1 MAPK3 PTHLH PTK2
20 respiratory system MP:0005388 9.81 FGFR2 FGFR3 FOXM1 HPSE JAK1 MAPK3
21 renal/urinary system MP:0005367 9.73 FGFR1 FGFR2 FGFR3 JAK1 PTHLH TYR
22 skeleton MP:0005390 9.7 FGFR1 FGFR2 FGFR3 FRS2 JAK1 MAPK3
23 vision/eye MP:0005391 9.28 FGFR1 FGFR2 FGFR3 FRS2 MAPK3 PTHLH

Drugs & Therapeutics for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Drugs for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 21)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Simvastatin Approved Phase 3 79902-63-9 54454
2 Lipid Regulating Agents Phase 3
3 Hydroxymethylglutaryl-CoA Reductase Inhibitors Phase 3
4 Hypolipidemic Agents Phase 3
5 Anticholesteremic Agents Phase 3
6 Antimetabolites Phase 3
7 Natriuretic Agents Phase 3
8 Natriuretic Peptide, C-Type Phase 3
9
Resveratrol Approved, Experimental, Investigational Phase 2 501-36-0 445154
10 Analgesics, Non-Narcotic Phase 2
11 Peripheral Nervous System Agents Phase 2
12 Antioxidants Phase 2
13 Antineoplastic Agents, Phytogenic Phase 2
14 Anti-Inflammatory Agents, Non-Steroidal Phase 2
15 Analgesics Phase 2
16 Protective Agents Phase 2
17 Platelet Aggregation Inhibitors Phase 2
18 Anti-Inflammatory Agents Phase 2
19 Antirheumatic Agents Phase 2
20
mometasone furoate Approved, Investigational, Vet_approved 83919-23-7
21 Mitogens

Interventional clinical trials:

(show all 23)
# Name Status NCT ID Phase Drugs
1 Treatment With HMG-COA Reductase Inhibitor (Simvastatin) of Growth and Bone Abnormalities in Children With Noonan Syndrome: A Phase III Randomised, Double Blind, Placebo-controlled Therapeutic Trial Recruiting NCT02713945 Phase 3 Simvastatin;Placebo
2 A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of BMN 111 in Children With Achondroplasia Active, not recruiting NCT03197766 Phase 3 BMN 111;Placebo
3 A Phase 3, Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia Enrolling by invitation NCT03424018 Phase 3 BMN 111
4 A Phase 2, Open-label, Sequential Cohort Dose-escalation Study of BMN 111 in Children With Achondroplasia Completed NCT02055157 Phase 2 BMN 111
5 A Phase 2, Open-Label, Extension Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of BMN 111 in Children With Achondroplasia Active, not recruiting NCT02724228 Phase 2 BMN 111
6 A Phase 2 Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of BMN 111 in Infants and Young Children With Achondroplasia, Age 0 to < 60 Months Enrolling by invitation NCT03583697 Phase 2 BMN 111;Placebo
7 A Phase 2 Open-Label Long-Term Extension Study to Evaluate the Safety and Efficacy of BMN 111 in Children With Achondroplasia Enrolling by invitation NCT03989947 Phase 2 Active BMN 111: Daily subcutaneous injection of 15 ug/kg of BMN 111
8 Resveratrol Trial for Relief of Pain in Pseudoachondroplasia Not yet recruiting NCT03866200 Phase 2 resveratrol;Placebo
9 A Phase 1, Two-Part, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of BMN 111 Administered to Healthy Adult Volunteers Completed NCT01590446 Phase 1 BMN 111;Normal Saline
10 C-Type Natriuretic Peptide and Achondroplasia Completed NCT01541306
11 Specific Survey of Norditropin® in Achondroplasia: Survey for Long-term Application Completed NCT01516229 somatropin
12 Issues Surrounding Prenatal Genetic Testing for Achondroplasia Completed NCT00001536
13 Open-label, Multicenter, Observational, Non-intervention Study to Retrospectively Evaluate the Efficacy of Norditropin® (Adult Height) in Patients With Achondroplasia/Hypochondroplasia Enrolled in the GH-1941 Study [Follow-up Survey] Completed NCT01435629 somatropin
14 Clinical and Molecular Manifestations of Human Skeletal Dysplasias and Short Stature Completed NCT00001754
15 ACHieve: A Multi-center, Longitudinal, Observational Study of Children With Achondroplasia Recruiting NCT03875534
16 A Multi-center, Prospective, Longitudinal, Observational Study to Investigate the Clinical and Anthropometric Characteristics of Children With the Diagnosis Achondroplasia. Recruiting NCT03794609
17 Prospective Clinical Assessment Study in Children With Achondroplasia: The PROPEL Trial Recruiting NCT04035811
18 Lifetime Impact Study for Achondroplasia (LISA) Recruiting NCT03872531
19 The Impact of Achondroplasia on Quality of Life, Healthcare Resource Use, Clinical, Socio-economic and Psychosocial State of the Individual. Recruiting NCT03449368
20 Universal Haplotype-Based Non Invasive Prenatal Diagnosis by Linked-Read Sequencing (10XGenomicsā„¢ Technology) Recruiting NCT03622892
21 The Norwegian Adult Achondroplasia Study Active, not recruiting NCT03780153
22 A Multicenter, Multinational Clinical Assessment Study for Pediatric Patients With Achondroplasia Enrolling by invitation NCT01603095
23 Achondroplasia Natural History Multicenter Clinical Study Enrolling by invitation NCT02597881

Search NIH Clinical Center for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans

Cochrane evidence based reviews: achondroplasia

Genetic Tests for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Genetic tests related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

# Genetic test Affiliating Genes
1 Severe Achondroplasia with Developmental Delay and Acanthosis Nigricans 29 FGFR3

Anatomical Context for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

MalaCards organs/tissues related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

41
Skin, Brain, Bone, Heart, Testes, Cerebellum, Bone Marrow

Publications for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Articles related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

(show all 28)
# Title Authors PMID Year
1
Prenatal and postnatal presentation of severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) due to the FGFR3 Lys650Met mutation. 38 8
18076102 2008
2
Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice. 38 8
11406607 2001
3
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. 38 8
10377013 1999
4
A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene. 38 8
10053006 1999
5
Mutant FGFR3 associated with SADDAN disease causes cytoskeleton disorganization through PLCĪ³1/Src-mediated paxillin hyperphosphorylation. 38
29242050 2018
6
A new genus and species of scorpion from Burma [Myanmar] (Scorpiones: Scorpiopidae): Implications for the taxonomy of the family. 38
28668484 2017
7
Achondroplasia: Development, pathogenesis, and therapy. 38
27987249 2017
8
Mild achondroplasia/hypochondroplasia with acanthosis nigricans, normal development, and a p.Ser348Cys FGFR3 mutation. 38
28181399 2017
9
FGFR3-related condition: a skeletal dysplasia with similarities to thanatophoric dysplasia and SADDAN due to Lys650Met. 38
25119967 2015
10
The paradox of FGFR3 signaling in skeletal dysplasia: why chondrocytes growth arrest while other cells over proliferate. 38
24295726 2014
11
Suppression of severe achondroplasia with developmental delay and acanthosis nigricans by the p.Thr651Pro mutation. 38
24352917 2014
12
Hypochondroplasia, Acanthosis Nigricans, and Insulin Resistance in a Child with FGFR3 Mutation: Is It Just an Association? 38
25505998 2014
13
Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia. 38
24324705 2013
14
FGFR3 related skeletal dysplasias diagnosed prenatally by ultrasonography and molecular analysis: presentation of 17 cases. 38
21910223 2011
15
SADDAN syndrome. 38
22145492 2011
16
Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. 38
20034074 2010
17
Acanthosis nigricans and insulin sensitivity in patients with achondroplasia and hypochodroplasia due to FGFR3 mutations. 38
19622626 2009
18
Enumeration of the colony-forming units-fibroblast from mouse and human bone marrow in normal and pathological conditions. 38
19383412 2009
19
[Case of a Japanese female presenting severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) syndrome with a K650M mutation in the fibroblast growth factor receptor 3 gene]. 38
19039991 2008
20
Frequent activating FGFR2 mutations in endometrial carcinomas parallel germline mutations associated with craniosynostosis and skeletal dysplasia syndromes. 38
17525745 2007
21
Familial acanthosis nigricans due to K650T FGFR3 mutation. 38
17875876 2007
22
Sustained phosphorylation of mutated FGFR3 is a crucial feature of genetic dwarfism and induces apoptosis in the ATDC5 chondrogenic cell line via PLCgamma-activated STAT1. 38
17561467 2007
23
K644E/M FGFR3 mutants activate Erk1/2 from the endoplasmic reticulum through FRS2 alpha and PLC gamma-independent pathways. 38
16476447 2006
24
The kinase activity of fibroblast growth factor receptor 3 with activation loop mutations affects receptor trafficking and signaling. 38
15292251 2004
25
Novel fibroblast growth factor receptor 3 (FGFR3) mutations in bladder cancer previously identified in non-lethal skeletal disorders. 38
12461689 2002
26
Some chondrodysplasias with short limbs: molecular perspectives. 38
12357475 2002
27
Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype. 38
11055896 2000
28
The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. 38
10696568 2000

Variations for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

ClinVar genetic disease variations for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 FGFR3 NM_000142.4(FGFR3): c.1620C> G (p.Asn540Lys) single nucleotide variant Pathogenic rs28933068 4:1807371-1807371 4:1805644-1805644
2 FGFR3 NM_000142.4(FGFR3): c.746C> G (p.Ser249Cys) single nucleotide variant Pathogenic rs121913483 4:1803568-1803568 4:1801841-1801841
3 FGFR3 NM_000142.4(FGFR3): c.742C> T (p.Arg248Cys) single nucleotide variant Pathogenic rs121913482 4:1803564-1803564 4:1801837-1801837
4 FGFR3 NM_000142.4(FGFR3): c.1949A> C (p.Lys650Thr) single nucleotide variant Pathogenic rs121913105 4:1807890-1807890 4:1806163-1806163
5 FGFR3 NM_000142.4(FGFR3): c.749C> G (p.Pro250Arg) single nucleotide variant Pathogenic rs4647924 4:1803571-1803571 4:1801844-1801844
6 FGFR3 NM_000142.4(FGFR3): c.1138G> A (p.Gly380Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs28931614 4:1806119-1806119 4:1804392-1804392
7 FGFR3 NM_000142.4(FGFR3): c.1993G> T (p.Ala665Ser) single nucleotide variant Uncertain significance rs764892330 4:1808017-1808017 4:1806290-1806290
8 FGFR3 NM_000142.4(FGFR3): c.2153A> G (p.Asn718Ser) single nucleotide variant Uncertain significance rs139773438 4:1808395-1808395 4:1806668-1806668
9 FGFR3 NM_000142.4(FGFR3): c.200G> A (p.Gly67Asp) single nucleotide variant Uncertain significance rs369232922 4:1801071-1801071 4:1799344-1799344

UniProtKB/Swiss-Prot genetic disease variations for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans:

74
# Symbol AA change Variation ID SNP ID
1 FGFR3 p.Lys650Met VAR_004161 rs121913105

Expression for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Search GEO for disease gene expression data for Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans.

Pathways for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Pathways related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to KEGG:

37
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 Ras signaling pathway hsa04014
3 Rap1 signaling pathway hsa04015
4 PI3K-Akt signaling pathway hsa04151
5 Regulation of actin cytoskeleton hsa04810

Pathways related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

(show top 50) (show all 142)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
14.3 STAT1 SRC PXN PTK2B PTK2 PTHLH
2
Show member pathways
14.16 STAT1 SRC PTK2B PTK2 PLCG1 MAPK3
3
Show member pathways
14.01 STAT1 SRC PTK2B PTK2 PLCG1 MAPK3
4
Show member pathways
13.97 STAT1 SRC SNAI1 PXN PTK2B PTK2
5
Show member pathways
13.84 STAT1 SRC PXN PTK2B PTK2 PLCG1
6
Show member pathways
13.83 STAT1 SRC PLCG1 MAPK3 FRS2 FGFR3
7
Show member pathways
13.7 SRC PXN PTK2B PTK2 PLCG1 MAPK3
8
Show member pathways
13.68 STAT1 SRC PXN PTK2B MAPK3 JAK1
9
Show member pathways
13.65 SRC PTK2 PLCG1 MAPK3 JAK1 FRS2
10
Show member pathways
13.57 SRC PLCG1 MAPK3 FRS2 FGFR3 FGFR2
11
Show member pathways
13.52 STAT1 SRC PXN PTK2B PTK2 PLCG1
12
Show member pathways
13.51 STAT1 SRC PXN PTK2B PTK2 PLCG1
13
Show member pathways
13.45 SRC PLCG1 MAPK3 FGFR3 FGFR2 FGFR1
14
Show member pathways
13.44 STAT1 SRC PTK2B PTK2 PLCG1 MAPK3
15
Show member pathways
13.41 SRC PLCG1 MAPK3 FGFR3 FGFR2 FGFR1
16
Show member pathways
13.35 SRC SNAI1 PXN PTK2B PTK2 PLCG1
17
Show member pathways
13.13 STAT1 SRC PXN PTK2B PTK2 PLCG1
18
Show member pathways
13.13 STAT1 PXN PTK2 MAPK3 JAK1 FGFR3
19
Show member pathways
13.12 SRC PXN PTK2B PTK2 PLCG1 MAPK3
20
Show member pathways
13.11 SRC PXN PTK2B PTK2 PLCG1 MAPK3
21
Show member pathways
13.1 SRC PTK2B PTK2 FGFR3 FGFR2 FGFR1
22
Show member pathways
13.08 STAT1 PTK2B PTK2 PLCG1 MAPK3 JAK1
23
Show member pathways
13.06 SRC PXN PTK2B PTK2 PLCG1 MAPK3
24
Show member pathways
13.04 STAT1 SRC PXN PTK2B PTK2 PLCG1
25
Show member pathways
13.03 STAT1 SRC PTK2B PTK2 MAPK3 JAK1
26
Show member pathways
13.03 STAT1 SRC PXN PTK2 MAPK3 JAK1
27
Show member pathways
13.02 SRC PXN PTK2B PTK2 PLCG1 MAPK3
28
Show member pathways
13 SRC PTK2B PTK2 PLCG1 MAPK3 JAK1
29
Show member pathways
12.98 PLCG1 FRS2 FGFR3 FGFR2 FGFR1 FGF1
30
Show member pathways
12.98 STAT1 SRC PXN PTK2 MAPK3 FRS2
31 12.98 STAT1 PTK2 PLCG1 MAPK3 JAK1 FGFR3
32
Show member pathways
12.9 SRC PLCG1 MAPK3 FGFR3 FGFR2 FGFR1
33 12.87 MAPK3 FGFR3 FGFR2 FGFR1 FGF1
34
Show member pathways
12.87 PLCG1 MAPK3 FGFR2 FGFR1 FGF1
35
Show member pathways
12.87 SRC PLCG1 MAPK3 FRS2 FGFR3 FGFR2
36
Show member pathways
12.86 SRC SNAI1 PXN PTK2B PTK2 PLCG1
37
Show member pathways
12.82 SRC PXN PTK2B PTK2 PLCG1 MAPK3
38
Show member pathways
12.82 SRC PTK2 PLCG1 MAPK3 JAK1 FGFR3
39
Show member pathways
12.81 FGFR3 FGFR2 FGFR1 FGF13 FGF1
40
Show member pathways
12.78 SRC PTK2B PTK2 PLCG1 MAPK3
41
Show member pathways
12.77 SRC PXN PTK2B PTK2 PLCG1
42
Show member pathways
12.77 STAT1 SRC PTK2 PLCG1 MAPK3 JAK1
43
Show member pathways
12.77 STAT1 SRC PXN PTK2B PTK2 MAPK3
44
Show member pathways
12.75 SRC SNAI1 PXN PTK2 MAPK3
45
Show member pathways
12.73 SRC PLCG1 MAPK3 FRS2 FGFR3 FGFR2
46
Show member pathways
12.71 SRC PXN PTK2 PLCG1 MAPK3
47 12.71 SRC PXN PTK2 MAPK3 FGFR3 FGFR2
48
Show member pathways
12.69 SRC PXN PTK2B PTK2 MAPK3
49
Show member pathways
12.65 STAT1 SRC PXN PTK2 PLCG1 MAPK3
50
Show member pathways
12.63 PXN MAPK3 FGFR3 FGFR2 FGFR1

GO Terms for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

Cellular components related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 focal adhesion GO:0005925 9.8 PXN PTK2B PTK2 MAPK3 JAK1 FGFR3
2 lamellipodium GO:0030027 9.67 PXN PTK2B PTK2 PLCG1
3 cytoplasm GO:0005737 9.55 TYR STAT1 SRC SNAI1 PXN PTK2B
4 cell cortex GO:0005938 9.35 PXN PTK2B PTK2 FGFR2 FGF1
5 nucleus GO:0005634 10.16 TYR STAT1 SRC SNAI1 PTK2B PTK2
6 cytosol GO:0005829 10.03 TYR STAT1 SRC SNAI1 PXN PTK2B

Biological processes related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

(show top 50) (show all 61)
# Name GO ID Score Top Affiliating Genes
1 cell migration GO:0016477 9.97 SRC SNAI1 PLCG1 FGFR1
2 angiogenesis GO:0001525 9.97 PTK2B PTK2 FGFR2 FGFR1 FGF1
3 axon guidance GO:0007411 9.97 SRC PTK2 PLCG1 MAPK3 FRS2
4 cell differentiation GO:0030154 9.94 SRC PTK2B PTK2 FGF1
5 Fc-gamma receptor signaling pathway involved in phagocytosis GO:0038096 9.92 SRC PTK2 PLCG1 MAPK3
6 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.91 SRC PTK2B MAPK3 FGFR3 FGFR2
7 transforming growth factor beta receptor signaling pathway GO:0007179 9.9 SRC PXN PTK2
8 lung development GO:0030324 9.9 FGFR2 FGFR1 FGF1
9 integrin-mediated signaling pathway GO:0007229 9.9 SRC PTK2B PTK2
10 protein autophosphorylation GO:0046777 9.88 SRC PTK2B PTK2 FGFR3 FGFR2 FGFR1
11 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.87 SRC PTK2 FGFR1
12 response to mechanical stimulus GO:0009612 9.86 STAT1 SRC PTK2B
13 vascular endothelial growth factor receptor signaling pathway GO:0048010 9.86 SRC PXN PTK2B PTK2
14 positive regulation of MAP kinase activity GO:0043406 9.85 SRC FGFR1 FGF1
15 cellular response to transforming growth factor beta stimulus GO:0071560 9.84 SRC PTK2 FGFR2
16 epidermal growth factor receptor signaling pathway GO:0007173 9.84 SRC PTK2B PTK2 PLCG1
17 response to hydrogen peroxide GO:0042542 9.83 STAT1 SRC PTK2B
18 response to cAMP GO:0051591 9.82 TYR STAT1 PTK2B
19 bone mineralization GO:0030282 9.8 PTHLH FGFR3 FGFR2
20 negative regulation of apoptotic process GO:0043066 9.8 SRC PTK2B PTK2
21 cellular response to reactive oxygen species GO:0034614 9.79 SRC PXN MAPK3
22 endothelial cell migration GO:0043542 9.77 STAT1 PXN PTK2
23 positive regulation of mesenchymal cell proliferation GO:0002053 9.77 STAT1 FGFR2 FGFR1
24 peptidyl-tyrosine autophosphorylation GO:0038083 9.76 SRC PTK2B PTK2 MAPK3
25 positive regulation of DNA biosynthetic process GO:2000573 9.73 SRC PTK2B
26 interleukin-6-mediated signaling pathway GO:0070102 9.73 STAT1 JAK1
27 positive regulation of phosphatidylinositol 3-kinase activity GO:0043552 9.73 SRC PTK2B PTK2 FGFR3
28 fibroblast growth factor receptor signaling pathway GO:0008543 9.73 MAPK3 FRS2 FGFR3 FGFR2 FGFR1 FGF1
29 regulation of osteoblast differentiation GO:0045667 9.72 PTK2 FGFR2
30 regulation of interferon-gamma-mediated signaling pathway GO:0060334 9.72 STAT1 JAK1
31 positive regulation of phospholipase C activity GO:0010863 9.72 PLCG1 FGFR1
32 organ induction GO:0001759 9.72 FRS2 FGFR1 FGF1
33 growth hormone receptor signaling pathway GO:0060396 9.71 PXN PTK2
34 cellular response to fluid shear stress GO:0071498 9.71 SRC PTK2B
35 branching involved in salivary gland morphogenesis GO:0060445 9.71 FGFR2 FGFR1
36 interleukin-35-mediated signaling pathway GO:0070757 9.71 STAT1 JAK1
37 interleukin-2-mediated signaling pathway GO:0038110 9.71 PTK2B JAK1
38 interleukin-27-mediated signaling pathway GO:0070106 9.7 STAT1 JAK1
39 mesenchymal cell differentiation GO:0048762 9.7 FGFR2 FGFR1
40 positive regulation of phospholipase activity GO:0010518 9.7 FGFR3 FGFR2 FGFR1
41 peptidyl-tyrosine phosphorylation GO:0018108 9.7 SRC PTK2B PTK2 JAK1 FGFR3 FGFR2
42 outer ear morphogenesis GO:0042473 9.69 MAPK3 FGFR1
43 interleukin-9-mediated signaling pathway GO:0038113 9.69 STAT1 JAK1
44 positive regulation of intracellular signal transduction GO:1902533 9.68 SRC FGF1
45 lung-associated mesenchyme development GO:0060484 9.68 FGFR2 FGFR1
46 interleukin-21-mediated signaling pathway GO:0038114 9.68 STAT1 JAK1
47 regulation of early endosome to late endosome transport GO:2000641 9.66 SRC MAPK3
48 endochondral bone growth GO:0003416 9.66 FGFR3 FGFR2
49 regulation of epithelial cell migration GO:0010632 9.65 SRC PTK2
50 prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis GO:0060527 9.65 FRS2 FGFR2

Molecular functions related to Achondroplasia, Severe, with Developmental Delay and Acanthosis Nigricans according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 protein kinase binding GO:0019901 9.92 SRC PXN PTK2 PLCG1 FOXM1
2 kinase activity GO:0016301 9.92 SRC PTK2B PTK2 MAPK3 JAK1 FGFR3
3 ubiquitin protein ligase binding GO:0031625 9.86 SRC PXN PTK2B JAK1
4 nucleotide binding GO:0000166 9.8 PTK2B PTK2 MAPK3 JAK1 FGFR3 FGFR2
5 protein phosphatase binding GO:0019903 9.72 PXN PTK2 JAK1
6 transmembrane receptor protein tyrosine kinase activity GO:0004714 9.67 FGFR3 FGFR2 FGFR1
7 non-membrane spanning protein tyrosine kinase activity GO:0004715 9.67 SRC PTK2B PTK2 JAK1
8 fibroblast growth factor binding GO:0017134 9.58 FGFR3 FGFR2 FGFR1
9 protein kinase activity GO:0004672 9.56 SRC PTK2B PTK2 MAPK3 JAK1 FGFR3
10 CCR5 chemokine receptor binding GO:0031730 9.51 STAT1 JAK1
11 neurotrophin TRKA receptor binding GO:0005168 9.48 PLCG1 FRS2
12 fibroblast growth factor-activated receptor activity GO:0005007 9.33 FGFR3 FGFR2 FGFR1
13 protein tyrosine kinase activity GO:0004713 9.17 SRC PTK2B PTK2 JAK1 FGFR3 FGFR2
14 protein binding GO:0005515 10.39 TYR STAT1 SRC SNAI1 PXN PTK2B
15 transferase activity GO:0016740 10.14 SRC PTK2B PTK2 MAPK3 JAK1 FGFR3
16 ATP binding GO:0005524 10.06 SRC PTK2B PTK2 MAPK3 JAK1 FGFR3

Sources for Achondroplasia, Severe, with Developmental Delay and Acanthosis...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 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
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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