eRAM
encyclopedia of Rare Disease Annotation for Precision Medicine
| hypochondroplasia | ||||
| Disease ID | 518 |
|---|---|
| Disease | hypochondroplasia |
| Definition | An autosomal dominant disorder that is often caused by a defect in fibroblast growth factor receptor 3, and characterized by short stature, micromelia, and a comparatively large head. The features are milder than those seen in achondroplasia. |
| Synonym | hch hypochondrodysplasia hypochondroplasia (disorder) |
| Orphanet | |
| OMIM | |
| DOID | |
| UMLS | C0410529 |
| SNOMED-CT | |
| Curated Gene | Entrez_id | Symbol | Resource(Total Genes:1) |
| Inferring Gene | (Waiting for update.) |
| Text Mined Gene | Entrez_id | Symbol | Score | Resource(Total Genes:18) 57492 | ARID1B | 2.12 | DISEASES 1280 | COL2A1 | 2.677 | DISEASES 1385 | CREB1 | 1.315 | DISEASES 2200 | FBN1 | 1.125 | DISEASES 2246 | FGF1 | 2.029 | DISEASES 8822 | FGF17 | 2.688 | DISEASES 2248 | FGF3 | 3.398 | DISEASES 2260 | FGFR1 | 2.534 | DISEASES 2263 | FGFR2 | 3.586 | DISEASES 2261 | FGFR3 | 7.375 | DISEASES 3481 | IGF2 | 1.057 | DISEASES 142678 | MIB2 | 3.08 | DISEASES 4882 | NPR2 | 2.44 | DISEASES 64324 | NSD1 | 1.758 | DISEASES 6473 | SHOX | 3.581 | DISEASES 6772 | STAT1 | 2.67 | DISEASES 100038246 | TLX1NB | 4.029 | DISEASES 7525 | YES1 | 2.247 | DISEASES |
| Locus | Symbol | Locus(Total Locus:1) FGFR3 | 4p16.3 |
| Disease ID | 518 |
|---|---|
| Disease | hypochondroplasia |
| Integrated Phenotype | HPO | Name(Total Integrated Phenotypes:20) HP:0001831 | Short toe HP:0009811 | Abnormality of the elbow HP:0000944 | Abnormality of the metaphyses HP:0003312 | Abnormal form of the vertebral bodies HP:0002970 | Genu varum HP:0002652 | Skeletal dysplasia HP:0000256 | Macrocephaly HP:0006487 | Bowing of the long bones HP:0003307 | Hyperlordosis HP:0003416 | Spinal canal stenosis HP:0002650 | Scoliosis HP:0005692 | Joint hyperflexibility HP:0010535 | Sleep apnea HP:0002758 | Osteoarthritis HP:0001156 | Brachydactyly syndrome HP:0002823 | Abnormality of the femur HP:0011405 | Childhood onset short-limb short stature HP:0002644 | Abnormality of pelvic girdle bone morphology HP:0002983 | Micromelia HP:0001249 | Intellectual disability |
| Text Mined Phenotype | HPO | Name | Sentences' Count(Total Phenotypes:3) |
| Disease ID | 518 |
|---|---|
| Disease | hypochondroplasia |
| Manually Symptom | (Waiting for update.) |
| Text Mined Symptom | (Waiting for update.) |
Manually Genotype(Total Manually Genotypes:1) | |||
|---|---|---|---|
| Gene | Mutation | DOI | Article Title |
| FGFR3 | c.1620C>G, p.N540K | doi:10.1038/gim.2015.129 | Comprehensive genetic exploration of skeletal dysplasia using targeted exome sequencing |
Text Mining Genotype(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
All Snps(Total Genotypes:38) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| snpId | pubmedId | geneId | geneSymbol | diseaseId | sourceId | sentence | score | Year | geneSymbol_dbSNP | CHROMOSOME | POS | REF | ALT |
| rs121913105 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1806163 | A | C,T |
| rs121913114 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1801930 | A | T |
| rs121913115 | 24411048 | 2261 | FGFR3 | umls:C0410529 | BeFree | Detection of a de novo Y278C mutation in FGFR3 in a pregnancy with severe fetal hypochondroplasia: prenatal diagnosis and literature review. | 0.494929303 | 2013 | FGFR3 | 4 | 1801928 | A | G |
| rs121913115 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1801928 | A | G |
| rs121913116 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1799395 | C | T |
| rs28928868 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1806164 | G | C,T |
| rs28931614 | 10360392 | 2261 | FGFR3 | umls:C0410529 | BeFree | The father has achondroplasia due to the common G1138A (G380R) mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, while the mother has hypochondroplasia due to the C1620G (N450K) mutation in the FGFR3 gene. | 0.494929303 | 1999 | FGFR3 | 4 | 1804392 | G | A,C |
| rs28931614 | 9853502 | 2261 | FGFR3 | umls:C0410529 | BeFree | To determine whether the genotype could be distinguished on the basis of the phenotype, we analysed height, arm span, and skeletal radiographs from 23 patients with achondroplasia and the G380R mutation of FGFR3 and eight with hypochondroplasia and the N540K mutation. | 0.494929303 | 1998 | FGFR3 | 4 | 1804392 | G | A,C |
| rs28931614 | 15345118 | 2261 | FGFR3 | umls:C0410529 | BeFree | This assay, which is performed on the LightCycler thermocycler, enables the rapid and reliable detection of the two most common FGFR3 mutations associated with ACH (1138G --> A and 1138G --> C; G380R) and HYCH (1620C --> A and 1620 C --> G; N540K) in a single test. | 0.494929303 | 2004 | FGFR3 | 4 | 1804392 | G | A,C |
| rs28933068 | 11071087 | 2261 | FGFR3 | umls:C0410529 | BeFree | Asn540Lys mutation in fibroblast growth factor receptor 3 and phenotype in hypochondroplasia. | 0.494929303 | 2000 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 15345118 | 2261 | FGFR3 | umls:C0410529 | BeFree | This assay, which is performed on the LightCycler thermocycler, enables the rapid and reliable detection of the two most common FGFR3 mutations associated with ACH (1138G --> A and 1138G --> C; G380R) and HYCH (1620C --> A and 1620 C --> G; N540K) in a single test. | 0.494929303 | 2004 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 22137367 | 2261 | FGFR3 | umls:C0410529 | BeFree | A pilot study of discontinuous, insulin-like growth factor 1-dosing growth hormone treatment in young children with FGFR3 N540K-mutated hypochondroplasia. | 0.494929303 | 2012 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 11055896 | 2261 | FGFR3 | umls:C0410529 | BeFree | Other mutations within the FGFR3 tyrosine kinase domain (e.g., C1620A or C1620G [both resulting in Asn540Lys]) are known to cause hypochondroplasia, a relatively common but milder skeletal dysplasia. | 0.494929303 | 2000 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 16020314 | 2261 | FGFR3 | umls:C0410529 | BeFree | Genetic analysis revealed two germline mutations, a seven base-pair deletion in exon 12 (G70313-703129del) in one allele of the retinoblastoma gene (RB1) and the N540K (C1620C > A) mutation in one allele of the fibroblast growth factor 3 (FGFR3) gene, a frequent mutation in hypochondroplasia. | 0.494929303 | 2005 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 23149434 | 2261 | FGFR3 | umls:C0410529 | BeFree | Hypochondroplasia in a child with 1620C>G (Asn540Lys) mutation in FGFR3. | 0.494929303 | 2012 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 9842995 | 2261 | FGFR3 | umls:C0410529 | BeFree | Our patient demonstrated one of the common FGFR3 mutations identified in hypochondroplasia, a C-to-A change at nucleotide 1620 (C1620A) in the tyrosine kinase domain. | 0.494929303 | 1998 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 7670477 | 2261 | FGFR3 | umls:C0410529 | UNIPROT | A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. | 0.494929303 | 1995 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 9055906 | 2261 | FGFR3 | umls:C0410529 | BeFree | Although most cases of hypochondroplasia were accounted for by a recurrent missense substitution (Asn540Lys) in the first tyrosine kinase domain of FGFR-3, a significant proportion (40%) of the patients in the present study did not possess this Asn540Lys mutation. | 0.494929303 | 1996 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 9853502 | 2261 | FGFR3 | umls:C0410529 | BeFree | To determine whether the genotype could be distinguished on the basis of the phenotype, we analysed height, arm span, and skeletal radiographs from 23 patients with achondroplasia and the G380R mutation of FGFR3 and eight with hypochondroplasia and the N540K mutation. | 0.494929303 | 1998 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 22137367 | 3630 | INS | umls:C0410529 | BeFree | A pilot study of discontinuous, insulin-like growth factor 1-dosing growth hormone treatment in young children with FGFR3 N540K-mutated hypochondroplasia. | 0.000542884 | 2012 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 10360392 | 2261 | FGFR3 | umls:C0410529 | BeFree | The father has achondroplasia due to the common G1138A (G380R) mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, while the mother has hypochondroplasia due to the C1620G (N450K) mutation in the FGFR3 gene. | 0.494929303 | 1999 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 23165795 | 2261 | FGFR3 | umls:C0410529 | BeFree | Neuroimaging and neurological findings in patients with hypochondroplasia and FGFR3 N540K mutation. | 0.494929303 | 2012 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 21225389 | 2261 | FGFR3 | umls:C0410529 | BeFree | Hypochondroplasia due to FGFR3 gene mutation (N540K) and mosaic form of Down syndrome in the same patient. | 0.494929303 | 2011 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 9672519 | 2261 | FGFR3 | umls:C0410529 | BeFree | We screened 65 children with Hch diagnosed by clinical and radiologic criteria for 2 previously described mutations, C1620A and C1620C in FGFR3; 28 (43%) of 65 patients were heterozygous for the C1620A transversion resulting in lysine to asparagine substitution at codon 540 in the tyrosine kinase domain of FGFR3. | 0.494929303 | 1998 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs28933068 | 16575888 | 2261 | FGFR3 | umls:C0410529 | BeFree | Molecular genetic analysis carried out retrospectively revealed that both fetuses were heterozygous for the C1620A mutation resulting in N540K substitution in FGFR3, the most common mutation in HCH. | 0.494929303 | 2006 | FGFR3 | 4 | 1805644 | C | A,G,T |
| rs587778769 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1799488 | A | T |
| rs587778773 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1801886 | C | T |
| rs587778775 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1803785 | G | T |
| rs587778776 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1804396 | T | A |
| rs587778801 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1801518 | C | T |
| rs587778811 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1801896 | G | T |
| rs587778816 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1803731 | C | G |
| rs587778817 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1803744 | A | T |
| rs77722678 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1805643 | A | G,C |
| rs78311289 | 21510009 | 2261 | FGFR3 | umls:C0410529 | BeFree | Acanthosis nigricans and hypochondroplasia in a child with a K650Q mutation in FGFR3. | 0.494929303 | 2010 | FGFR3 | 4 | 1806162 | A | C,G |
| rs78311289 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1806162 | A | C,G |
| rs80053154 | NA | 2261 | FGFR3 | umls:C0410529 | CLINVAR | NA | 0.494929303 | NA | FGFR3 | 4 | 1805636 | A | G |
GWASdb Annotation(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
GWASdb Snp Trait(Total Genotypes:0) | |
|---|---|
| (Waiting for update.) | |
Mapped by lexical matching(Total Items:8) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0011405 | Childhood onset short-limb short stature | MP:0004708 | short lumbar vertebrae | reduced length of any or all of the six bony segments of the spine located anterior to the sacral vertebrae and posterior to the thoracic vertebrae |
| HP:0006487 | Bowing of the long bones | MP:0013621 | decreased internal diameter of femur | reduced cross-sectional distance that extends from one lateral edge of the femur long bone marrow cavity, through its center and to the opposite lateral edge of the bone marrow cavity through the mid point of the femur |
| HP:0002644 | Abnormality of pelvic girdle bone morphology | MP:0013620 | increased internal diameter of femur | increased cross-sectional distance that extends from one lateral edge of the femur long bone marrow cavity, through its center and to the opposite lateral edge of the bone marrow cavity through the mid point of the femur |
| HP:0000944 | Abnormality of the metaphyses | MP:0013621 | decreased internal diameter of femur | reduced cross-sectional distance that extends from one lateral edge of the femur long bone marrow cavity, through its center and to the opposite lateral edge of the bone marrow cavity through the mid point of the femur |
| HP:0002823 | Abnormality of the femur | MP:0020010 | decreased bone mineral density of femur | reduction in the quatitative measurment value of mineral content of bone in the long bone of the thigh |
| HP:0003416 | Spinal canal stenosis | MP:0010884 | esophagus stenosis | abnormal narrowing or constriction of the esophagus |
| HP:0003312 | Abnormal form of the vertebral bodies | MP:0020010 | decreased bone mineral density of femur | reduction in the quatitative measurment value of mineral content of bone in the long bone of the thigh |
| HP:0009811 | Abnormality of the elbow | MP:0008158 | increased diameter of femur | increased width of the cross-sectional distance that extends from one lateral edge of the femur, through its center and to the opposite lateral edge |
Mapped by homologous gene(Total Items:20) | ||||
|---|---|---|---|---|
| HP ID | HP Name | MP ID | MP Name | Annotation |
| HP:0002650 | Scoliosis | MP:0020309 | increased creatine kinase activity | increased ability of to catalyze the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+). |
| HP:0009811 | Abnormality of the elbow | MP:0020039 | increased bone ossification | increase in the formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance |
| HP:0002970 | Genu varum | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0002758 | Osteoarthritis | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0003416 | Spinal canal stenosis | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0001156 | Brachydactyly syndrome | MP:0020157 | abnormal behavioral response to alcohol | any anomaly in the behavioral response induced by alcohol, such as induced hyperactivity or stereotypic behavior |
| HP:0002983 | Micromelia | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0000256 | Macrocephaly | MP:0020309 | increased creatine kinase activity | increased ability of to catalyze the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+). |
| HP:0005692 | Joint hyperflexibility | MP:0012125 | decreased bronchoconstrictive response | reduction in the expected bronchoconstrictive response to provocation challenge with lipopolysaccharide, bradykinin, histamine or other antigen/allergen or agent, often measured by plethysmography |
| HP:0003307 | Hyperlordosis | MP:0020309 | increased creatine kinase activity | increased ability of to catalyze the reaction: ATP + creatine = N-phosphocreatine + ADP + 2 H(+). |
| HP:0001831 | Short toe | MP:0020039 | increased bone ossification | increase in the formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance |
| HP:0002823 | Abnormality of the femur | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0011405 | Childhood onset short-limb short stature | MP:0020039 | increased bone ossification | increase in the formation of bone or of a bony substance, or the conversion of fibrous tissue or of cartilage into bone or a bony substance |
| HP:0002644 | Abnormality of pelvic girdle bone morphology | MP:0020254 | decreased collagen level | decreased level of the main structural protein of the various connective tissues in animals |
| HP:0001249 | Intellectual disability | MP:0020316 | decreased vascular endothelial cell proliferation | decrease in the expansion rate of any vascular endothelial cell population by cell division |
| HP:0010535 | Sleep apnea | MP:0020220 | decreased tear production | decreased production of the amount of fluid produced in the eye |
| HP:0006487 | Bowing of the long bones | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0000944 | Abnormality of the metaphyses | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0002652 | Skeletal dysplasia | MP:0020137 | decreased bone mineralization | decrease in the rate at which minerals are deposited into bone |
| HP:0003312 | Abnormal form of the vertebral bodies | MP:3000003 | abnormal Ebner's gland morphology | any structural anomaly of the serous salivary glands which reside adjacent to the moats surrounding the circumvallate and foliate papillae just anterior to the posterior third of the tongue, anterior to the terminal sulcus; these exocrine glands secrete l |
| Disease ID | 518 |
|---|---|
| Disease | hypochondroplasia |
| Case | (Waiting for update.) |