HPE9
MCID: HLP025
MIFTS: 27

Holoprosencephaly 9 (HPE9)

Categories: Endocrine diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Holoprosencephaly 9

MalaCards integrated aliases for Holoprosencephaly 9:

Name: Holoprosencephaly 9 58 12 76 30 6
Pituitary Anomalies with Holoprosencephaly-Like Features 58 12 76 74
Hpe9 58 12 76
Holoprosencephaly with Microphthalmia and First Branchial Arch Anomalies 58 12
Holoprosencephaly-9 76 13
Holoprosencephaly, Type 9 41

Characteristics:

OMIM:

58
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
variable expressivity
incomplete penetrance


HPO:

33
holoprosencephaly 9:
Onset and clinical course variable expressivity incomplete penetrance
Inheritance autosomal dominant inheritance sporadic


Classifications:



Summaries for Holoprosencephaly 9

OMIM : 58 Holoprosencephaly-9 refers to a disorder characterized by a wide phenotypic spectrum of brain developmental defects, with or without overt forebrain cleavage abnormalities. It usually includes midline craniofacial anomalies involving the first branchial arch and/or orbits, pituitary hypoplasia with panhypopituitarism, and postaxial polydactyly. The disorder shows incomplete penetrance and variable expressivity (summary by Roessler et al., 2003 and Bertolacini et al., 2012). For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100). (610829)

MalaCards based summary : Holoprosencephaly 9, also known as pituitary anomalies with holoprosencephaly-like features, is related to culler-jones syndrome, and has symptoms including seizures An important gene associated with Holoprosencephaly 9 is GLI2 (GLI Family Zinc Finger 2). Affiliated tissues include pituitary and brain, and related phenotypes are short stature and malar flattening

Disease Ontology : 12 A holoprosencephaly that has material basis in heterozygous mutation in the GLI2 gene on chromosome 2q14.

UniProtKB/Swiss-Prot : 76 Holoprosencephaly 9: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. Holoprosencephaly type 9 is characterized by defective anterior pituitary formation and pan-hypopituitarism, with or without overt forebrain cleavage abnormalities, and holoprosencephaly-like midfacial hypoplasia.

Related Diseases for Holoprosencephaly 9

Diseases in the Holoprosencephaly family:

Holoprosencephaly 3 Holoprosencephaly 4
Holoprosencephaly 2 Holoprosencephaly 1
Holoprosencephaly 6 Holoprosencephaly 8
Holoprosencephaly 5 Holoprosencephaly 7
Holoprosencephaly 9 Holoprosencephaly 11
Nonsyndromic Holoprosencephaly

Diseases related to Holoprosencephaly 9 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 culler-jones syndrome 11.2

Symptoms & Phenotypes for Holoprosencephaly 9

Human phenotypes related to Holoprosencephaly 9:

33 (show all 34)
# Description HPO Frequency HPO Source Accession
1 short stature 33 occasional (7.5%) HP:0004322
2 malar flattening 33 HP:0000272
3 hydrocephalus 33 HP:0000238
4 seizures 33 HP:0001250
5 macrotia 33 HP:0000400
6 dental malocclusion 33 HP:0000689
7 global developmental delay 33 HP:0001263
8 depressed nasal bridge 33 HP:0005280
9 microcephaly 33 HP:0000252
10 cryptorchidism 33 HP:0000028
11 optic nerve hypoplasia 33 HP:0000609
12 short philtrum 33 HP:0000322
13 microphthalmia 33 HP:0000568
14 hypoplasia of the maxilla 33 HP:0000327
15 midface retrusion 33 HP:0011800
16 holoprosencephaly 33 HP:0001360
17 hypotelorism 33 HP:0000601
18 partial agenesis of the corpus callosum 33 HP:0001338
19 postaxial hand polydactyly 33 HP:0001162
20 anophthalmia 33 HP:0000528
21 micropenis 33 HP:0000054
22 panhypopituitarism 33 HP:0000871
23 single median maxillary incisor 33 HP:0006315
24 short hard palate 33 HP:0010290
25 bilateral cleft lip and palate 33 HP:0002744
26 hypoplasia of the premaxilla 33 HP:0010650
27 growth hormone deficiency 33 HP:0000824
28 abnormal cortical gyration 33 HP:0002536
29 single naris 33 HP:0009932
30 anterior pituitary agenesis 33 HP:0010626
31 agenesis of incisor 33 HP:0006485
32 anterior pituitary hypoplasia 33 HP:0010627
33 underdeveloped tragus 33 HP:0011272
34 prominent antihelix 33 HP:0000395

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
holoprosencephaly
anterior pituitary hypoplasia
delayed psychomotor development

Head And Neck Mouth:
cleft palate
cleft lip

Head And Neck Eyes:
optic nerve hypoplasia
microphthalmia
hypotelorism
anophthalmia

Endocrine Features:
hypopituitarism

Skeletal Feet:
postaxial polydactyly

Head And Neck Nose:
flat nasal bridge
single nares

Head And Neck Ears:
prominent antihelix
first branchial arch anomalies
abnormal ears
abnormal helix
hypoplastic tragus

Head And Neck Head:
microcephaly

Genitourinary Internal Genitalia Male:
cryptorchidism

Genitourinary External Genitalia Male:
micropenis

Skeletal Hands:
postaxial polydactyly

Head And Neck Face:
midface hypoplasia
temporomandibular joint abnormalities
first branchial arch anomalies

Growth Height:
short stature (in some patients)

Head And Neck Teeth:
solitary median maxillary central incisor

Clinical features from OMIM:

610829

UMLS symptoms related to Holoprosencephaly 9:


seizures

Drugs & Therapeutics for Holoprosencephaly 9

Search Clinical Trials , NIH Clinical Center for Holoprosencephaly 9

Genetic Tests for Holoprosencephaly 9

Genetic tests related to Holoprosencephaly 9:

# Genetic test Affiliating Genes
1 Holoprosencephaly 9 30 GLI2

Anatomical Context for Holoprosencephaly 9

MalaCards organs/tissues related to Holoprosencephaly 9:

42
Pituitary, Brain

Publications for Holoprosencephaly 9

Articles related to Holoprosencephaly 9:

# Title Authors Year
1
Clinical findings in patients with GLI2 mutations--phenotypic variability. ( 21204792 )
2012
2
Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly. ( 20685856 )
2010
3
GLI2 mutations in four Brazilian patients: how wide is the phenotypic spectrum? ( 17096318 )
2006
4
A previously unidentified amino-terminal domain regulates transcriptional activity of wild-type and disease-associated human GLI2. ( 15994174 )
2005
5
Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. ( 14581620 )
2003

Variations for Holoprosencephaly 9

ClinVar genetic disease variations for Holoprosencephaly 9:

6 (show top 50) (show all 55)
# Gene Variation Type Significance SNP ID Assembly Location
1 GLI2 NM_005270.4(GLI2): c.1323G> A (p.Trp441Ter) single nucleotide variant Pathogenic rs121917707 GRCh38 Chromosome 2, 120975064: 120975064
2 GLI2 GLI2, 1-BP DEL, NT2274 deletion Pathogenic
3 GLI2 NM_005270.4(GLI2): c.1323G> A (p.Trp441Ter) single nucleotide variant Pathogenic rs121917707 GRCh37 Chromosome 2, 121732640: 121732640
4 GLI2 NM_005270.4(GLI2): c.1435C> G (p.Arg479Gly) single nucleotide variant Pathogenic rs121917708 GRCh37 Chromosome 2, 121736076: 121736076
5 GLI2 NM_005270.4(GLI2): c.1435C> G (p.Arg479Gly) single nucleotide variant Pathogenic rs121917708 GRCh38 Chromosome 2, 120978500: 120978500
6 GLI2 NM_005270.4(GLI2): c.4663T> C (p.Ser1555Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs144372453 GRCh37 Chromosome 2, 121748153: 121748153
7 GLI2 NM_005270.4(GLI2): c.4663T> C (p.Ser1555Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs144372453 GRCh38 Chromosome 2, 120990577: 120990577
8 GLI2 NM_005270.4(GLI2): c.864_865delCC (p.His289Profs) deletion Pathogenic rs398122882 GRCh37 Chromosome 2, 121727987: 121727988
9 GLI2 NM_005270.4(GLI2): c.864_865delCC (p.His289Profs) deletion Pathogenic rs398122882 GRCh38 Chromosome 2, 120970411: 120970412
10 GLI2 NM_005270.4(GLI2): c.1885G> A (p.Glu629Lys) single nucleotide variant Pathogenic rs387907277 GRCh37 Chromosome 2, 121742248: 121742248
11 GLI2 NM_005270.4(GLI2): c.1885G> A (p.Glu629Lys) single nucleotide variant Pathogenic rs387907277 GRCh38 Chromosome 2, 120984672: 120984672
12 GLI2 NM_005270.4(GLI2): c.4558G> A (p.Asp1520Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs114814747 GRCh37 Chromosome 2, 121748048: 121748048
13 GLI2 NM_005270.4(GLI2): c.4558G> A (p.Asp1520Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs114814747 GRCh38 Chromosome 2, 120990472: 120990472
14 GLI2 NM_005270.4(GLI2): c.3943C> T (p.Pro1315Ser) single nucleotide variant Benign/Likely benign rs114376238 GRCh37 Chromosome 2, 121747433: 121747433
15 GLI2 NM_005270.4(GLI2): c.3943C> T (p.Pro1315Ser) single nucleotide variant Benign/Likely benign rs114376238 GRCh38 Chromosome 2, 120989857: 120989857
16 GLI2 NM_005270.4(GLI2): c.3048C> T (p.Asp1016=) single nucleotide variant Benign/Likely benign rs140479803 GRCh37 Chromosome 2, 121746538: 121746538
17 GLI2 NM_005270.4(GLI2): c.3048C> T (p.Asp1016=) single nucleotide variant Benign/Likely benign rs140479803 GRCh38 Chromosome 2, 120988962: 120988962
18 GLI2 NM_005270.4(GLI2): c.2940C> T (p.Ser980=) single nucleotide variant Benign/Likely benign rs146811565 GRCh37 Chromosome 2, 121746430: 121746430
19 GLI2 NM_005270.4(GLI2): c.2940C> T (p.Ser980=) single nucleotide variant Benign/Likely benign rs146811565 GRCh38 Chromosome 2, 120988854: 120988854
20 GLI2 NM_005270.4(GLI2): c.4054A> G (p.Met1352Val) single nucleotide variant Benign/Likely benign rs149140724 GRCh37 Chromosome 2, 121747544: 121747544
21 GLI2 NM_005270.4(GLI2): c.4054A> G (p.Met1352Val) single nucleotide variant Benign/Likely benign rs149140724 GRCh38 Chromosome 2, 120989968: 120989968
22 GLI2 NM_005270.4(GLI2): c.1120C> T (p.Arg374Cys) single nucleotide variant Uncertain significance rs200076785 GRCh37 Chromosome 2, 121729577: 121729577
23 GLI2 NM_005270.4(GLI2): c.1120C> T (p.Arg374Cys) single nucleotide variant Uncertain significance rs200076785 GRCh38 Chromosome 2, 120972001: 120972001
24 GLI2 NM_005270.4(GLI2): c.1294G> A (p.Val432Met) single nucleotide variant Benign/Likely benign rs142296407 GRCh37 Chromosome 2, 121732611: 121732611
25 GLI2 NM_005270.4(GLI2): c.1294G> A (p.Val432Met) single nucleotide variant Benign/Likely benign rs142296407 GRCh38 Chromosome 2, 120975035: 120975035
26 GLI2 NM_005270.4(GLI2): c.963C> G (p.Pro321=) single nucleotide variant Benign/Likely benign rs149894186 GRCh38 Chromosome 2, 120970510: 120970510
27 GLI2 NM_005270.4(GLI2): c.963C> G (p.Pro321=) single nucleotide variant Benign/Likely benign rs149894186 GRCh37 Chromosome 2, 121728086: 121728086
28 GLI2 NM_005270.4(GLI2): c.1761G> A (p.Thr587=) single nucleotide variant Benign/Likely benign rs61732852 GRCh38 Chromosome 2, 120984548: 120984548
29 GLI2 NM_005270.4(GLI2): c.1761G> A (p.Thr587=) single nucleotide variant Benign/Likely benign rs61732852 GRCh37 Chromosome 2, 121742124: 121742124
30 GLI2 NM_005270.4(GLI2): c.3882G> A (p.Thr1294=) single nucleotide variant Benign/Likely benign rs115052795 GRCh38 Chromosome 2, 120989796: 120989796
31 GLI2 NM_005270.4(GLI2): c.3882G> A (p.Thr1294=) single nucleotide variant Benign/Likely benign rs115052795 GRCh37 Chromosome 2, 121747372: 121747372
32 GLI2 NM_005270.4(GLI2): c.2554G> A (p.Ala852Thr) single nucleotide variant Uncertain significance rs751028726 GRCh37 Chromosome 2, 121746044: 121746044
33 GLI2 NM_005270.4(GLI2): c.2554G> A (p.Ala852Thr) single nucleotide variant Uncertain significance rs751028726 GRCh38 Chromosome 2, 120988468: 120988468
34 GLI2 NM_005270.4(GLI2): c.2990C> G (p.Pro997Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs563818052 GRCh37 Chromosome 2, 121746480: 121746480
35 GLI2 NM_005270.4(GLI2): c.2990C> G (p.Pro997Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs563818052 GRCh38 Chromosome 2, 120988904: 120988904
36 GLI2 NM_005270.4(GLI2): c.891delG (p.Gln297Hisfs) deletion Pathogenic rs1057518696 GRCh38 Chromosome 2, 120970438: 120970438
37 GLI2 NM_005270.4(GLI2): c.3261dupC (p.Thr1088Hisfs) duplication Pathogenic rs1057518689 GRCh38 Chromosome 2, 120989175: 120989175
38 GLI2 NM_005270.4(GLI2): c.3261dupC (p.Thr1088Hisfs) duplication Pathogenic rs1057518689 GRCh37 Chromosome 2, 121746751: 121746751
39 GLI2 NM_005270.4(GLI2): c.4654A> T (p.Thr1552Ser) single nucleotide variant Likely pathogenic rs1057518657 GRCh37 Chromosome 2, 121748144: 121748144
40 GLI2 NM_005270.4(GLI2): c.4654A> T (p.Thr1552Ser) single nucleotide variant Likely pathogenic rs1057518657 GRCh38 Chromosome 2, 120990568: 120990568
41 GLI2 NM_005270.4(GLI2): c.891delG (p.Gln297Hisfs) deletion Pathogenic rs1057518696 GRCh37 Chromosome 2, 121728014: 121728014
42 GLI2 NM_005270.4(GLI2): c.4198G> T (p.Gly1400Cys) single nucleotide variant Uncertain significance rs143914758 GRCh38 Chromosome 2, 120990112: 120990112
43 GLI2 NM_005270.4(GLI2): c.4198G> T (p.Gly1400Cys) single nucleotide variant Uncertain significance rs143914758 GRCh37 Chromosome 2, 121747688: 121747688
44 GLI2 NM_005270.4(GLI2): c.1541A> C (p.Tyr514Ser) single nucleotide variant Uncertain significance rs1553477146 GRCh38 Chromosome 2, 120982738: 120982738
45 GLI2 NM_005270.4(GLI2): c.1541A> C (p.Tyr514Ser) single nucleotide variant Uncertain significance rs1553477146 GRCh37 Chromosome 2, 121740314: 121740314
46 GLI2 NM_005270.4(GLI2): c.4332_4333delGCinsAT (p.Met1444_Leu1445delinsIlePhe) indel Benign rs1553479775 GRCh38 Chromosome 2, 120990246: 120990247
47 GLI2 NM_005270.4(GLI2): c.4332_4333delGCinsAT (p.Met1444_Leu1445delinsIlePhe) indel Benign rs1553479775 GRCh37 Chromosome 2, 121747822: 121747823
48 GLI2 NM_005270.4(GLI2): c.451G> C (p.Ala151Pro) single nucleotide variant Uncertain significance rs781771721 GRCh38 Chromosome 2, 120951439: 120951439
49 GLI2 NM_005270.4(GLI2): c.451G> C (p.Ala151Pro) single nucleotide variant Uncertain significance rs781771721 GRCh37 Chromosome 2, 121709015: 121709015
50 GLI2 NM_005270.4(GLI2): c.192dup (p.Asp65Terfs) duplication Pathogenic GRCh37 Chromosome 2, 121684980: 121684980

Expression for Holoprosencephaly 9

Search GEO for disease gene expression data for Holoprosencephaly 9.

Pathways for Holoprosencephaly 9

GO Terms for Holoprosencephaly 9

Sources for Holoprosencephaly 9

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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