MCID: MCR013
MIFTS: 60

Microphthalmia

Categories: Eye diseases, Fetal diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Microphthalmia

MalaCards integrated aliases for Microphthalmia:

Name: Microphthalmia 12 74 20 43 36 29 54 6 15 39 17
Microphthalmos 12 43 44 32
Isolated Anophthalmia-Microphthalmia Syndrome 20 58 6
Isolated Microphthalmia-Anophthalmia-Coloboma 20 58
Microphthalmia-Anophthalmia-Coloboma Spectrum 20
Isolated Anophthalmia - Microphthalmia 20
Isolated Pure Microphthalmia 20
Primitive Anophthalmia 20
Anophthalmia, Clinical 6
Simple Microphthalmos 12
Clinical Anophthalmia 20
Mac Spectrum 20

Characteristics:

Orphanet epidemiological data:

58
isolated microphthalmia-anophthalmia-coloboma
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: 1-9/100000 (Europe); Age of onset: Infancy,Neonatal; Age of death: normal life expectancy;

Classifications:

Orphanet: 58  
Rare eye diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:10629
KEGG 36 H01027
ICD9CM 34 743.1
MeSH 44 D008850
NCIt 50 C98989
SNOMED-CT 67 156902006
ICD10 32 Q11.2
ICD10 via Orphanet 33 Q11.0 Q11.1 Q11.2
Orphanet 58 ORPHA2542
UMLS 71 C0026010

Summaries for Microphthalmia

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2542DefinitionA non-syndromic group of structural developmental eye defects characterized by the variable combination of microphthalmia, ocular coloboma, and anophthalmia, either unilaterally or bilaterally, with no other associated ocular conditions in the affected/contralateral eye, and no systemic anomalies.EpidemiologyThe prevalence of microphthalmia is 1:7,000, anophthalmia is 1:30,000 and coloboma is 1:5,000 live births, with combined prevalence 3-30:100,000 births. Associated malformations affect 32-93% of the patients. There is no clear predilection for ethnicity or gender.Clinical descriptionMicrophthalmia-anophthalmia-coloboma (MAC) consists of phenotypic continuum of congenital eye defects that are manifest at birth. In some cases, such as retinal coloboma or mild microphthalmia, detection may occur later in life. True anophthalmia is the abortion of eye development at the developing optic vesicle stage (3-4 weeks gestation) leading to absence of the eye, optic nerve and chiasm. Commonly clinical anophthalmia (also referred to as severe microphthalmia) occurs, where a small cystic remnant is detectable on pathology/imaging. Nanophthalmos and posterior microphthalmia, are rare subsets of microphthalmia, where overall the eye is structurally normal but it has a reduced axial length of <20 mm with high hypermetropia. Ocular coloboma may involve the inferonasal aspect of the eye, including the iris, ciliary body, zonules, retina, retinal pigment epithelium (RPE), choroid and/or optic disc.EtiologyMAC has a complex etiology, with monogenic, chromosomal and environmental causes. SOX2, OTX2 and STRA6 variants account for 75% of bilateral anophthalmia/severe microphthalmia. Chromosomal abnormalities account for 20-30% of MAC. Environmental factors associated with anophthalmia include maternally-acquired infections, smoking and perinatal exposure to certain medications. Maternal vitamin A deficiency, alcohol abuse and use of teratogenic drugs during pregnancy have been linked to coloboma and microphthalmia.Diagnostic methodsPostnatal diagnosis can be made through clinical examination, with confirmation of true/clinical anophthalmia through MRI brain and orbit imaging. Molecular diagnosis can be made through genetic testing, such as array comparative genomic hybridization (aCGH) or whole exome/genome sequencing.Differential diagnosisDifferential diagnoses includes aniridia, anterior segment dysgenesis, congenital corneal opacity, sclerocornea, cryptophthalmos, cyclopia and congenital cystic eye. MAC may also occur as part of various syndromes, and thus examination by specialists for the presence of systemic features (e.g. associated neurological or pituitary defects) is recommended. Genetic diagnosis may aid the identification of potential systemic anomalies.Antenatal diagnosisPrenatal diagnosis of anophthalmia or microphthalmia may be made through 2D or 3D ultrasonography during the second trimester (or 12 weeks post-conception with a transvaginal ultrasound) or fetal magnetic resonance imaging to visualize the orbit.Genetic counselingGenetic counselling can be challenging due to the range of known genetic causes and phenotypic variability. Prediction of inheritance pattern is often difficult, due to de novo changes, mosaicism and non-penetrance. If a genetic diagnosis is established, informed family planning advice can be provided including prenatal and preimplantation diagnosis.Management and treatmentThere is no treatment for MAC patients. They should be managed by a multidisciplinary team of specialists, including ophthalmologists, pediatricians and clinical geneticists. If there is visual potential, children should be monitored to maximize vision by correcting refractive error or squints, and preventing amblyopia. Fundus examinations are required in patients with chorioretinal coloboma as it is associated with a risk of retinal detachment. Low vision should be supported using visual aids. Significant microphthalmic or anophthalmic eyes may undergo socket expansion using enlarging cosmetic shells/conformers to minimize facial deformity.PrognosisIsolated MAC are structural birth defects with no treatment available.Visit the Orphanet disease page for more resources.

MalaCards based summary : Microphthalmia, also known as microphthalmos, is related to microphthalmia, syndromic 3 and microphthalmia, syndromic 1. An important gene associated with Microphthalmia is VSX2 (Visual System Homeobox 2), and among its related pathways/superpathways are Mesodermal Commitment Pathway and Neural Crest Differentiation. Affiliated tissues include eye, skin and retina, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

Disease Ontology : 12 An eye disease where one or both eyeballs are abnormally small.

MedlinePlus Genetics : 43 Microphthalmia is an eye abnormality that arises before birth. In this condition, one or both eyeballs are abnormally small. In some affected individuals, the eyeball may appear to be completely missing; however, even in these cases some remaining eye tissue is generally present. Such severe microphthalmia should be distinguished from another condition called anophthalmia, in which no eyeball forms at all. However, the terms anophthalmia and severe microphthalmia are often used interchangeably. Microphthalmia may or may not result in significant vision loss.People with microphthalmia may also have a condition called coloboma. Colobomas are missing pieces of tissue in structures that form the eye. They may appear as notches or gaps in the colored part of the eye called the iris; the retina, which is the specialized light-sensitive tissue that lines the back of the eye; the blood vessel layer under the retina called the choroid; or in the optic nerves, which carry information from the eyes to the brain. Colobomas may be present in one or both eyes and, depending on their size and location, can affect a person's vision.People with microphthalmia may also have other eye abnormalities, including clouding of the lens of the eye (cataract) and a narrowed opening of the eye (narrowed palpebral fissure). Additionally, affected individuals may have an abnormality called microcornea, in which the clear front covering of the eye (cornea) is small and abnormally curved.Between one-third and one-half of affected individuals have microphthalmia as part of a syndrome that affects other organs and tissues in the body. These forms of the condition are described as syndromic. When microphthalmia occurs by itself, it is described as nonsyndromic or isolated.

KEGG : 36 Anophthalmia and/or microphthalmia (A/M) can be defined as an absence or reduced size of the globe in the orbit. Anophthalmia refers to complete absence of the globe in the presence of ocular adnexae. Microphthalmia is defined as a globe with a total axial length that is at least two standard deviations below the mean for age. Coloboma, or a defect in the closure of the choroid fissure, is most common ocular malformation associated with microphthalmia. Coloboma is considered to be part of the A/M spectrum. A/M can be isolated, associated other anomalies or part of a well defined syndrome. A/M have complex aetiology with chromosomal, monogenic and environmental causes identified.

Wikipedia : 74 Microphthalmia (Greek: μικρός mikros = small; ὀφθαλμός ophthalmos = eye), also referred as... more...

Related Diseases for Microphthalmia

Diseases related to Microphthalmia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 617)
# Related Disease Score Top Affiliating Genes
1 microphthalmia, syndromic 3 33.9 VSX2 STRA6 SOX2 SIX6 RAX PAX6
2 microphthalmia, syndromic 1 33.7 VSX2 STRA6 HCCS BCOR
3 linear skin defects with multiple congenital anomalies 1 33.7 RAX PAX6 HCCS BCOR
4 microphthalmia, syndromic 9 33.6 VSX2 STRA6 RBP4 HCCS GDF6 ALDH1A3
5 microphthalmia, syndromic 8 33.6 VSX2 STRA6 SOX2 RAX PAX6 OTX2
6 microphthalmia, syndromic 6 33.5 RAX PAX6 GDF6 BMP4
7 coloboma of macula 33.4 VSX2 TFAP2A TENM3 STRA6 SOX2 SIX6
8 microphthalmia, isolated 2 33.3 VSX2 STRA6 SOX2 RAX PAX6 OTX2
9 microphthalmia, isolated 3 33.3 VSX2 STRA6 SOX2 RAX PAX6 OTX2
10 microphthalmia, syndromic 5 33.3 RAX OTX2
11 syndromic microphthalmia 33.3 VSX2 STRA6 SOX2 SIX6 PAX6 OTX2
12 colobomatous microphthalmia 33.3 VSX2 TFAP2A TENM3 STRA6 RBP4 RAX
13 fryns microphthalmia syndrome 33.2 VSX2 SOX2 PAX6 OTX2
14 microphthalmia, isolated 8 33.0 ALDH1A3-AS1 ALDH1A3
15 microphthalmia, isolated, with coloboma 6 33.0 GDF6 GDF3
16 microphthalmia, isolated 6 33.0 VSX2 PRSS56
17 isolated microphthalmia 33.0 VSX2 STRA6 SIX6 RAX PRSS56 OTX2
18 peters-plus syndrome 32.3 VSX2 STRA6 SOX2 PAX6 HCCS GDF6
19 nanophthalmos 32.3 VSX2 SIX6 PRSS56 PAX6 OTX2
20 cataract 31.9 VSX2 SOX2 SIX6 PAX6 OTX2 BMP4
21 sclerocornea 31.6 TENM3 SIX6 RAX PAX6 HCCS
22 aniridia 1 31.4 VSX2 SOX2 SIX6 RAX PAX6 OTX2
23 anterior segment dysgenesis 31.4 VSX2 TENM3 SIX6 PAX6 OTX2 GDF6
24 amblyopia 31.3 TFAP2A PRSS56 PAX6 OTX2
25 waardenburg's syndrome 31.2 PAX6 MITF BMP4
26 holoprosencephaly 31.2 SOX2 SIX6 PAX6 OTX2 BMP4
27 sox2 disorder 31.1 SOX2 SIX6
28 orbital cyst 31.1 RAX HCCS GDF6
29 fundus dystrophy 31.1 VSX2 STRA6 SOX2 SIX6 PRSS56 PAX6
30 coloboma of iris 31.0 TFAP2A PAX6
31 esotropia 31.0 TFAP2A PAX6 OTX2
32 optic nerve hypoplasia, bilateral 30.9 VSX2 SIX6 PAX6 OTX2
33 persistent hyperplastic primary vitreous 30.9 VSX2 PAX6 OTX2
34 retinitis pigmentosa 30.9 VSX2 SOX2 SIX6 PRSS56 PAX6 OTX2
35 hypopituitarism 30.7 SOX2 PAX6 OTX2
36 diaphragmatic hernia, congenital 30.7 STRA6 HCCS BMP4
37 septooptic dysplasia 30.6 SOX2 SIX6 PAX6 OTX2
38 axenfeld-rieger syndrome 30.6 VSX2 RAX PAX6 BMP4
39 congenital aphakia 30.5 VSX2 PAX6
40 pathologic nystagmus 30.4 TFAP2A SIX6 PAX6 OTX2
41 microphthalmia, syndromic 2 11.6
42 bosma arhinia microphthalmia syndrome 11.6
43 microphthalmia, syndromic 12 11.6
44 microphthalmia, syndromic 13 11.6
45 microphthalmia, isolated, with coloboma 9 11.6
46 microphthalmia/coloboma and skeletal dysplasia syndrome 11.6
47 microphthalmia, isolated 5 11.6
48 microphthalmia with limb anomalies 11.5
49 microphthalmia, syndromic 11 11.5
50 microphthalmia, syndromic 10 11.5

Graphical network of the top 20 diseases related to Microphthalmia:



Diseases related to Microphthalmia

Symptoms & Phenotypes for Microphthalmia

GenomeRNAi Phenotypes related to Microphthalmia according to GeneCards Suite gene sharing:

26 (show all 23)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-119 9.72 OTX2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-12 9.72 VSX2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-125 9.72 OTX2
4 Increased shRNA abundance (Z-score > 2) GR00366-A-127 9.72 MITF
5 Increased shRNA abundance (Z-score > 2) GR00366-A-128 9.72 MITF
6 Increased shRNA abundance (Z-score > 2) GR00366-A-15 9.72 MITF
7 Increased shRNA abundance (Z-score > 2) GR00366-A-152 9.72 HCCS
8 Increased shRNA abundance (Z-score > 2) GR00366-A-169 9.72 OTX2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-177 9.72 BCOR
10 Increased shRNA abundance (Z-score > 2) GR00366-A-2 9.72 OTX2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-202 9.72 MITF
12 Increased shRNA abundance (Z-score > 2) GR00366-A-206 9.72 OTX2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-210 9.72 BCOR
14 Increased shRNA abundance (Z-score > 2) GR00366-A-214 9.72 HCCS MITF VSX2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-22 9.72 MITF
16 Increased shRNA abundance (Z-score > 2) GR00366-A-26 9.72 VSX2
17 Increased shRNA abundance (Z-score > 2) GR00366-A-68 9.72 HCCS
18 Increased shRNA abundance (Z-score > 2) GR00366-A-75 9.72 MITF
19 Increased shRNA abundance (Z-score > 2) GR00366-A-77 9.72 VSX2
20 Increased shRNA abundance (Z-score > 2) GR00366-A-79 9.72 BCOR
21 Increased shRNA abundance (Z-score > 2) GR00366-A-91 9.72 VSX2
22 Increased shRNA abundance (Z-score > 2) GR00366-A-95 9.72 BCOR
23 Increased shRNA abundance (Z-score > 2) GR00366-A-99 9.72 OTX2

MGI Mouse Phenotypes related to Microphthalmia:

46 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 10.37 ALDH1A3 BCOR BMP4 DYRK1A GDF3 HCCS
2 embryo MP:0005380 10.29 ALDH1A3 BCOR BMP4 DYRK1A GDF3 HCCS
3 growth/size/body region MP:0005378 10.28 ALDH1A3 BCOR BMP4 DYRK1A GDF3 GDF6
4 mortality/aging MP:0010768 10.27 ALDH1A3 BCOR BMP4 DYRK1A GDF3 GDF6
5 nervous system MP:0003631 10.22 BCOR BMP4 DYRK1A GDF6 MITF OTX2
6 craniofacial MP:0005382 10.21 ALDH1A3 BMP4 GDF6 MITF OTX2 PAX6
7 endocrine/exocrine gland MP:0005379 10.2 ALDH1A3 BMP4 DYRK1A MITF OTX2 PAX6
8 digestive/alimentary MP:0005381 10.1 ALDH1A3 BMP4 OTX2 PAX6 RAX RBP4
9 normal MP:0002873 10 ALDH1A3 BMP4 GDF3 HCCS MITF OTX2
10 hearing/vestibular/ear MP:0005377 9.95 BMP4 GDF6 MITF OTX2 PAX6 SOX2
11 pigmentation MP:0001186 9.81 MITF OTX2 PAX6 PRSS56 RBP4 SOX2
12 skeleton MP:0005390 9.61 ALDH1A3 BMP4 GDF6 MITF OTX2 PAX6
13 vision/eye MP:0005391 9.47 ALDH1A3 BMP4 GDF6 MITF OTX2 PAX6

Drugs & Therapeutics for Microphthalmia

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 2 Study of ARQ 197 in Patients With Microphthalmia Transcription Factor Associated Tumors Completed NCT00557609 Phase 2 ARQ 197
2 Extensive Circumferential Partial Thickness Sclerectomy in Nanophthalmic Eyes Unknown status NCT03748732
3 Molecular Analysis of Microphthalmia/Anophthalmia and Related Disorders Completed NCT00011843
4 A Long-term Postoperative Outcome After Bilateral Congenital Cataract Surgery in Eyes With Microphthalmos Completed NCT01818037

Search NIH Clinical Center for Microphthalmia

Cochrane evidence based reviews: microphthalmos

Genetic Tests for Microphthalmia

Genetic tests related to Microphthalmia:

# Genetic test Affiliating Genes
1 Microphthalmia 29

Anatomical Context for Microphthalmia

MalaCards organs/tissues related to Microphthalmia:

40
Eye, Skin, Retina, Pituitary, Brain, Kidney, Bone Marrow

Publications for Microphthalmia

Articles related to Microphthalmia:

(show top 50) (show all 4051)
# Title Authors PMID Year
1
A genome-wide linkage scan in Tunisian families identifies a novel locus for non-syndromic posterior microphthalmia to chromosome 2q37.1. 54 61 6
19526372 2009
2
Mutations in the CHX10 gene in non-syndromic microphthalmia/anophthalmia patients from Qatar. 6 54 61
17661825 2007
3
CHX10 mutations cause non-syndromic microphthalmia/ anophthalmia in Arab and Jewish kindreds. 61 54 6
15257456 2004
4
Biometric and molecular characterization of clinically diagnosed posterior microphthalmos. 6 61
23127749 2013
5
ALDH1A3 mutations cause recessive anophthalmia and microphthalmia. 61 6
23312594 2013
6
Alteration of the serine protease PRSS56 causes angle-closure glaucoma in mice and posterior microphthalmia in humans and mice. 6 61
21532570 2011
7
Posterior microphthalmos as a genetically heterogeneous condition that can be allelic to nanophthalmos. 6 61
21670352 2011
8
Autosomal-recessive posterior microphthalmos is caused by mutations in PRSS56, a gene encoding a trypsin-like serine protease. 6 61
21397065 2011
9
Mutations in a novel serine protease PRSS56 in families with nanophthalmos. 61 6
21850159 2011
10
Mutation of the bone morphogenetic protein GDF3 causes ocular and skeletal anomalies. 61 6
19864492 2010
11
Confirmation of RAX gene involvement in human anophthalmia. 6 61
18783408 2008
12
Mutations in the human RAX homeobox gene in a patient with anophthalmia and sclerocornea. 6 61
14662654 2004
13
Human microphthalmia associated with mutations in the retinal homeobox gene CHX10. Percin EF, Ploder LA, Yu JJ, Arici K, Horsford DJ, Rutherford A, Bapat B, Cox DW, Duncan AMV, Kalnins VI, Kocak-Altintas A, Sowden JC, Trabousli E, Sarfarazi M, McInnes RR.*(1) Nat Gen 2000;25:397-401. 6 61
11341888 2001
14
Isolated "clinical anophthalmia" in an extensively affected Arab kindred. 61 6
3378363 1988
15
Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. 6
23307924 2013
16
Incomplete penetrance and phenotypic variability characterize Gdf6-attributable oculo-skeletal phenotypes. 6
19129173 2009
17
Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. 6
18425797 2008
18
Hereditary high hypermetropia in the Faroe Islands. 6
15823920 2005
19
Involvement of MITF-A, an alternative isoform of mi transcription factor, on the expression of tryptase gene in human mast cells. 61 54
20513998 2010
20
Microphthalmia, parkinsonism, and enhanced nociception in Pitx3 ( 416insG ) mice. 61 54
20033184 2010
21
Microphthalmia in Texel sheep is associated with a missense mutation in the paired-like homeodomain 3 (PITX3) gene. 61 54
20084168 2010
22
Association of a de novo 16q copy number variant with a phenotype that overlaps with Lenz microphthalmia and Townes-Brocks syndromes. 61 54
20003547 2009
23
Complex regulation of tartrate-resistant acid phosphatase (TRAP) expression by interleukin 4 (IL-4): IL-4 indirectly suppresses receptor activator of NF-kappaB ligand (RANKL)-mediated TRAP expression but modestly induces its expression directly. 61 54
19801646 2009
24
BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects. 54 61
19367324 2009
25
Mutations in the newly identified RAX regulatory sequence are not a frequent cause of micro/anophthalmia. 61 54
19397404 2009
26
Epithelioid angiomyolipoma of the kidney. 61 54
19121090 2009
27
A new locus for congenital cataract, microcornea, microphthalmia, and atypical iris coloboma maps to chromosome 2. 61 54
19004499 2009
28
Diadenosine tetraphosphate hydrolase is part of the transcriptional regulation network in immunologically activated mast cells. 54 61
18644867 2008
29
Induction of microphthalmia transcription factor (Mitf) by forskolin and stimulation of melanin release in UISO-Mel-6 cells. 61 54
18028952 2008
30
Expression patterns of MITF during human cutaneous embryogenesis: evidence for bulge epithelial expression and persistence of dermal melanoblasts. 54 61
18312434 2008
31
Molecular analysis of CHX10 and MFRP in Chinese subjects with primary angle closure glaucoma and short axial length eyes. 54 61
18648522 2008
32
Schwannoma of the kidney. 54 61
18391921 2008
33
PNL2 melanocytic marker in immunohistochemical evaluation of primary mucosal melanoma of the head and neck. 54 61
18228523 2008
34
SOX2 plays a critical role in the pituitary, forebrain, and eye during human embryonic development. 54 61
18285410 2008
35
Overexpression of Pax6 results in microphthalmia, retinal dysplasia and defective retinal ganglion cell axon guidance. 61 54
18507827 2008
36
Mutation in a novel connexin-like gene (Gjf1) in the mouse affects early lens development and causes a variable small-eye phenotype. 61 54
18385072 2008
37
Unique effects of KIT D816V in BaF3 cells: induction of cluster formation, histamine synthesis, and early mast cell differentiation antigens. 61 54
18390729 2008
38
Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression. 54 61
18385377 2008
39
[Mutation screening of MITF gene in patients with Waardenburg syndrome type 2]. 54 61
18424413 2008
40
Sclerosing PEComa: clinicopathologic analysis of a distinctive variant with a predilection for the retroperitoneum. 54 61
18223480 2008
41
Gene expression signature associated with BRAF mutations in human primary cutaneous melanomas. 61 54
19383316 2008
42
Clear cell sarcoma of soft tissue: a clinicopathologic, immunohistochemical, and molecular analysis of 33 cases. 61 54
18300804 2008
43
Identification of novel mutations and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia. 61 54
18385794 2008
44
Cutaneous melanocytoneuroma: the first case of a distinctive intraneural tumor with dual nerve sheath and melanocytic differentiation. 61 54
17997740 2007
45
[Tumors showing perivascular epithelioid cell differentiation: a clinicopathologic study of 39 cases]. 54 61
18261305 2007
46
SOX2 anophthalmia syndrome: 12 new cases demonstrating broader phenotype and high frequency of large gene deletions. 54 61
17522144 2007
47
Anophthalmia and microphthalmia. 61 54
18039390 2007
48
Functional analysis of human mutations in homeodomain transcription factor PITX3. 54 61
17888164 2007
49
HCCS loss-of-function missense mutation in a female with bilateral microphthalmia and sclerocornea: a novel gene for severe ocular malformations? 54 61
17893649 2007
50
Inherited PAX6, NF1 and OTX2 mutations in a child with microphthalmia and aniridia. 54 61
17406642 2007

Variations for Microphthalmia

ClinVar genetic disease variations for Microphthalmia:

6 (show top 50) (show all 345)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RAX NM_013435.3(RAX):c.439C>T (p.Gln147Ter) SNV Pathogenic 7635 rs104894663 18:56939697-56939697 18:59272465-59272465
2 RAX NM_013435.3(RAX):c.575G>A (p.Arg192Gln) SNV Pathogenic 7636 rs121909127 18:56936702-56936702 18:59269470-59269470
3 RAX NM_013435.3(RAX):c.909C>G (p.Tyr303Ter) SNV Pathogenic 7638 rs121909128 18:56936368-56936368 18:59269136-59269136
4 GDF6 NM_001001557.4(GDF6):c.758A>T (p.Gln253Leu) SNV Pathogenic 8375 rs121909355 8:97157401-97157401 8:96145173-96145173
5 GDF6 NM_001001557.4(GDF6):c.980C>A (p.Pro327His) SNV Pathogenic 8376 rs121909356 8:97157179-97157179 8:96144951-96144951
6 VSX2 CHX10, 4-KB DEL, EXON 3 Deletion Pathogenic 14863
7 GDF3 NM_020634.3(GDF3):c.914T>C (p.Leu305Pro) SNV Pathogenic 30592 rs387906945 12:7842655-7842655 12:7690059-7690059
8 GDF3 NM_020634.3(GDF3):c.584G>A (p.Arg195Gln) SNV Pathogenic 30593 rs146973734 12:7842985-7842985 12:7690389-7690389
9 ALDH1A3 NM_000693.4(ALDH1A3):c.265C>T (p.Arg89Cys) SNV Pathogenic 40203 rs397514652 15:101427837-101427837 15:100887632-100887632
10 VSX2 NM_182894.3(VSX2):c.267del (p.Gln90fs) Deletion Pathogenic 849052 14:74706531-74706531 14:74239828-74239828
11 PRSS56 NM_001195129.2(PRSS56):c.926G>C (p.Trp309Ser) SNV Pathogenic 31079 rs387907095 2:233388202-233388202 2:232523492-232523492
12 PRSS56 NM_001195129.2(PRSS56):c.526C>G (p.Arg176Gly) SNV Pathogenic 31080 rs387907096 2:233387304-233387304 2:232522594-232522594
13 PRSS56 NM_001195129.2(PRSS56):c.958G>A (p.Gly320Arg) SNV Pathogenic 183170 rs730882158 2:233388234-233388234 2:232523524-232523524
14 PRSS56 NM_001195129.2(PRSS56):c.709G>A (p.Gly237Arg) SNV Pathogenic 183173 rs730882160 2:233387772-233387772 2:232523062-232523062
15 PRSS56 NM_001195129.2(PRSS56):c.1183T>C (p.Cys395Arg) SNV Pathogenic 183174 rs730882161 2:233388652-233388652 2:232523942-232523942
16 PRSS56 NM_001195129.2(PRSS56):c.1555G>A (p.Gly519Arg) SNV Pathogenic 183175 rs730882162 2:233389959-233389959 2:232525249-232525249
17 RAX NM_013435.3(RAX):c.664del (p.Ser222fs) Deletion Pathogenic 7637 rs1603388837 18:56936613-56936613 18:59269381-59269381
18 VSX2 NM_182894.3(VSX2):c.210del (p.Ala71fs) Deletion Pathogenic 937573 14:74706471-74706471 14:74239768-74239768
19 PRSS56 NM_001195129.2(PRSS56):c.833dup (p.Val279fs) Duplication Pathogenic 183172 rs730882159 2:233387890-233387891 2:232523180-232523181
20 VSX2 NM_182894.3(VSX2):c.397C>T (p.Arg133Ter) SNV Pathogenic 933553 14:74707911-74707911 14:74241208-74241208
21 PRSS56 NM_001195129.2(PRSS56):c.1202C>A (p.Ala401Glu) SNV Pathogenic 915448 2:233388764-233388764 2:232524054-232524054
22 VSX2 NC_000014.9:g.(?_74239552)_(74245298_?)del Deletion Pathogenic 645368 14:74706255-74712001 14:74239552-74245298
23 ALDH1A3-AS1 NM_000693.4(ALDH1A3):c.1477G>C (p.Ala493Pro) SNV Pathogenic 40204 rs397514653 15:101454916-101454916 15:100914711-100914711
24 ALDH1A3-AS1 NM_000693.4(ALDH1A3):c.475+1G>T SNV Pathogenic 40205 rs78931658 15:101432845-101432845 15:100892640-100892640
25 PRSS56 NM_001195129.2(PRSS56):c.1066dup (p.Gln356fs) Duplication Pathogenic 31077 rs730882064 2:233388527-233388528 2:232523817-232523818
26 GDF6 NM_001001557.4(GDF6):c.746C>A (p.Ala249Glu) SNV Pathogenic 8371 rs121909352 8:97157413-97157413 8:96145185-96145185
27 PAX6 NM_000280.4(PAX6):c.131G>C (p.Arg44Pro) SNV Pathogenic 430901 rs1554985722 11:31824262-31824262 11:31802714-31802714
28 RBP4 NM_006744.4(RBP4):c.394T>A (p.Tyr132Asn) SNV Pathogenic 430902 rs1329285216 10:95353754-95353754 10:93593997-93593997
29 TFAP2A NM_001032280.3(TFAP2A):c.1019_1020del (p.Lys340fs) Deletion Pathogenic 523459 rs1554110735 6:10398926-10398927 6:10398693-10398694
30 VSX2 NM_182894.3(VSX2):c.679C>T (p.Arg227Trp) SNV Pathogenic 14862 rs121912545 14:74726404-74726404 14:74259701-74259701
31 SIX6 NM_007374.3(SIX6):c.-227_572+235del Deletion Pathogenic 637953 14:60975886-60976919 14:60509168-60510201
32 DYRK1A NM_001347721.2(DYRK1A):c.586C>T (p.Arg196Ter) SNV Pathogenic 162153 rs724159949 21:38858865-38858865 21:37486563-37486563
33 ALDH1A3 NM_000693.4(ALDH1A3):c.287G>A (p.Arg96His) SNV Pathogenic 978214 15:101427859-101427859 15:100887654-100887654
34 ALDH1A3-AS1 NM_000693.4(ALDH1A3):c.709G>A (p.Gly237Arg) SNV Pathogenic 978215 15:101436180-101436180 15:100895975-100895975
35 OTX2 NM_021728.4(OTX2):c.296C>A (p.Ala99Asp) SNV Pathogenic 430900 rs1555350254 14:57269051-57269051 14:56802333-56802333
36 VSX2 NM_182894.3(VSX2):c.599G>C (p.Arg200Pro) SNV Pathogenic/Likely pathogenic 14861 rs121912543 14:74726324-74726324 14:74259621-74259621
37 ALDH1A3-AS1 NM_000693.4(ALDH1A3):c.1436G>A (p.Gly479Asp) SNV Likely pathogenic 585293 rs1567174297 15:101448657-101448657 15:100908452-100908452
38 PRSS56 NM_001195129.2(PRSS56):c.94del (p.Gln32fs) Deletion Likely pathogenic 932138 2:233385402-233385402 2:232520692-232520692
39 VSX2 NM_182894.3(VSX2):c.162C>A (p.Asp54Glu) SNV Conflicting interpretations of pathogenicity 468358 rs61747367 14:74706426-74706426 14:74239723-74239723
40 VSX2 NM_182894.3(VSX2):c.564G>A (p.Pro188=) SNV Conflicting interpretations of pathogenicity 738345 rs201354547 14:74711976-74711976 14:74245273-74245273
41 VSX2 NM_182894.3(VSX2):c.699C>T (p.Pro233=) SNV Conflicting interpretations of pathogenicity 705711 rs141712104 14:74726424-74726424 14:74259721-74259721
42 VSX2 NM_182894.3(VSX2):c.249G>A (p.Gly83=) SNV Conflicting interpretations of pathogenicity 706510 rs751526974 14:74706513-74706513 14:74239810-74239810
43 VSX2 NM_182894.3(VSX2):c.171C>G (p.Ala57=) SNV Conflicting interpretations of pathogenicity 706589 rs201395979 14:74706435-74706435 14:74239732-74239732
44 VSX2 NM_182894.3(VSX2):c.579G>A (p.Gln193=) SNV Conflicting interpretations of pathogenicity 314195 rs182972044 14:74711991-74711991 14:74245288-74245288
45 VSX2 NM_182894.3(VSX2):c.750G>A (p.Pro250=) SNV Conflicting interpretations of pathogenicity 314196 rs192712847 14:74726475-74726475 14:74259772-74259772
46 VSX2 NM_182894.3(VSX2):c.504C>T (p.Asn168=) SNV Conflicting interpretations of pathogenicity 468359 rs550984628 14:74711916-74711916 14:74245213-74245213
47 VSX2 NM_182894.3(VSX2):c.939T>A (p.Ala313=) SNV Conflicting interpretations of pathogenicity 314203 rs372651860 14:74727475-74727475 14:74260772-74260772
48 VSX2 NM_182894.3(VSX2):c.244G>A (p.Gly82Arg) SNV Conflicting interpretations of pathogenicity 285031 rs375294678 14:74706508-74706508 14:74239805-74239805
49 RAX NM_013435.3(RAX):c.197G>C (p.Arg66Thr) SNV Conflicting interpretations of pathogenicity 496932 rs536765190 18:56940242-56940242 18:59273010-59273010
50 RAX NM_013435.3(RAX):c.290-4C>A SNV Conflicting interpretations of pathogenicity 766849 rs200338566 18:56939850-56939850 18:59272618-59272618

Copy number variations for Microphthalmia from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 264074 X 6000000 9500000 Copy number Microphthalmia

Expression for Microphthalmia

Search GEO for disease gene expression data for Microphthalmia.

Pathways for Microphthalmia

GO Terms for Microphthalmia

Cellular components related to Microphthalmia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 chromatin GO:0000785 9.23 VSX2 TFAP2A SOX2 SIX6 RAX PAX6

Biological processes related to Microphthalmia according to GeneCards Suite gene sharing:

(show all 26)
# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 10.13 VSX2 TFAP2A SOX2 SIX6 RAX PAX6
2 positive regulation of transcription by RNA polymerase II GO:0045944 10.1 TFAP2A SOX2 RAX PAX6 OTX2 MITF
3 negative regulation of transcription by RNA polymerase II GO:0000122 10.04 VSX2 TFAP2A SOX2 PAX6 MITF BMP4
4 regulation of gene expression GO:0010468 9.92 SOX2 PAX6 MITF BMP4
5 heart development GO:0007507 9.88 STRA6 RBP4 BMP4 BCOR
6 positive regulation of transcription, DNA-templated GO:0045893 9.86 TFAP2A SOX2 PAX6 OTX2 MITF GDF6
7 multicellular organism development GO:0007275 9.85 VSX2 SOX2 SIX6 RAX PAX6 OTX2
8 visual perception GO:0007601 9.8 VSX2 SIX6 RBP4 RAX PAX6
9 lung development GO:0030324 9.79 STRA6 RBP4 BMP4
10 BMP signaling pathway GO:0030509 9.78 GDF6 GDF3 BMP4
11 negative regulation of epithelial cell proliferation GO:0050680 9.75 SOX2 PAX6 BMP4
12 SMAD protein signal transduction GO:0060395 9.74 GDF6 GDF3 BMP4
13 blood vessel development GO:0001568 9.71 STRA6 PAX6 BMP4
14 positive regulation of pathway-restricted SMAD protein phosphorylation GO:0010862 9.69 GDF6 GDF3 BMP4
15 forebrain development GO:0030900 9.67 SOX2 PAX6 OTX2 BMP4
16 pituitary gland development GO:0021983 9.65 SOX2 PAX6 BMP4
17 camera-type eye morphogenesis GO:0048593 9.63 TENM3 BMP4
18 pulmonary valve morphogenesis GO:0003184 9.62 STRA6 BMP4
19 cell fate commitment GO:0045165 9.62 SOX2 PAX6 MITF BMP4
20 eyelid development in camera-type eye GO:0061029 9.6 TFAP2A STRA6
21 smooth muscle tissue development GO:0048745 9.59 STRA6 BMP4
22 telencephalon regionalization GO:0021978 9.55 PAX6 BMP4
23 retinol transport GO:0034633 9.46 STRA6 RBP4
24 regulation of cell fate commitment GO:0010453 9.43 GDF3 BMP4
25 eye development GO:0001654 9.35 SOX2 SIX6 RBP4 PAX6 GDF3
26 camera-type eye development GO:0043010 9.1 STRA6 RAX PRSS56 PAX6 MITF BMP4

Molecular functions related to Microphthalmia according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 10.1 VSX2 TFAP2A SOX2 SIX6 RAX PAX6
2 DNA-binding transcription factor activity GO:0003700 9.88 TFAP2A SOX2 PAX6 OTX2 MITF
3 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.87 TFAP2A SOX2 SIX6 RAX PAX6 OTX2
4 DNA-binding transcription repressor activity, RNA polymerase II-specific GO:0001227 9.76 VSX2 TFAP2A PAX6 MITF
5 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.76 VSX2 TFAP2A SOX2 SIX6 RAX PAX6
6 sequence-specific double-stranded DNA binding GO:1990837 9.73 VSX2 TFAP2A SIX6 RAX PAX6 OTX2
7 transcription regulatory region sequence-specific DNA binding GO:0000976 9.67 TFAP2A SOX2 PAX6 BCOR
8 retinol binding GO:0019841 9.43 STRA6 RBP4
9 retinal binding GO:0016918 9.4 STRA6 RBP4
10 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.1 TFAP2A SOX2 RAX PAX6 OTX2 MITF
11 retinol transmembrane transporter activity GO:0034632 8.96 STRA6 RBP4

Sources for Microphthalmia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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