CPHD1
MCID: PTT045
MIFTS: 36

Pituitary Hormone Deficiency, Combined, 1 (CPHD1)

Categories: Genetic diseases, Rare diseases

Aliases & Classifications for Pituitary Hormone Deficiency, Combined, 1

MalaCards integrated aliases for Pituitary Hormone Deficiency, Combined, 1:

Name: Pituitary Hormone Deficiency, Combined, 1 56 73 29 13 6 71
Cphd1 56 52 73
Hormone Deficiency, Pituitary, Combined, Type 1 39
Pituitary Hormone Deficiency, Combined 1 52

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive
autosomal dominant


HPO:

31
pituitary hormone deficiency, combined, 1:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



Summaries for Pituitary Hormone Deficiency, Combined, 1

OMIM : 56 Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH; 139250) and one or more of the other 5 anterior pituitary hormones. Mutations of the POU1F1 gene in the human and Pit1 in the mouse are responsible for pleiotropic deficiencies of GH, prolactin (PRL; 176760), and thyroid-stimulating hormone (TSH; see 188540), while the production of adrenocorticotrophic hormone (ACTH; see 176830), luteinizing hormone (LH; 152780), and follicle-stimulating hormone (FSH; 136530) are preserved (Wu et al., 1998). In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen (Aarskog et al., 1997). Some cases present with severe mental retardation along with short stature (Radovick et al., 1992). (613038)

MalaCards based summary : Pituitary Hormone Deficiency, Combined, 1, also known as cphd1, is related to adamantinous craniopharyngioma and frontotemporal dementia, chromosome 3-linked. An important gene associated with Pituitary Hormone Deficiency, Combined, 1 is POU1F1 (POU Class 1 Homeobox 1). Affiliated tissues include pituitary, eye and thyroid, and related phenotypes are macroglossia and intellectual disability

UniProtKB/Swiss-Prot : 73 Pituitary hormone deficiency, combined, 1: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD1 is characterized by pleiotropic deficiencies of growth hormone, prolactin and thyroid-stimulating hormone, while the production of adrenocorticotropic hormone, luteinizing hormone, and follicle-stimulating hormone are preserved. In infancy severe growth deficiency from birth as well as distinctive facial features with prominent forehead, marked midfacial hypoplasia with depressed nasal bridge, deep-set eyes, and a short nose with anteverted nostrils and hypoplastic pituitary gland by MRI examination can be seen. Some cases present with severe mental retardation along with short stature.

Related Diseases for Pituitary Hormone Deficiency, Combined, 1

Graphical network of the top 20 diseases related to Pituitary Hormone Deficiency, Combined, 1:



Diseases related to Pituitary Hormone Deficiency, Combined, 1

Symptoms & Phenotypes for Pituitary Hormone Deficiency, Combined, 1

Human phenotypes related to Pituitary Hormone Deficiency, Combined, 1:

31 (show all 18)
# Description HPO Frequency HPO Source Accession
1 macroglossia 31 HP:0000158
2 intellectual disability 31 HP:0001249
3 depressed nasal bridge 31 HP:0005280
4 muscular hypotonia 31 HP:0001252
5 short nose 31 HP:0003196
6 anteverted nares 31 HP:0000463
7 short stature 31 HP:0004322
8 hypothyroidism 31 HP:0000821
9 prominent forehead 31 HP:0011220
10 frontal bossing 31 HP:0002007
11 jaundice 31 HP:0000952
12 deeply set eye 31 HP:0000490
13 malar flattening 31 HP:0000272
14 midface retrusion 31 HP:0011800
15 delayed cranial suture closure 31 HP:0000270
16 severe postnatal growth retardation 31 HP:0008850
17 prolonged neonatal jaundice 31 HP:0006579
18 generalized hypotonia 31 HP:0001290

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Nose:
depressed nasal bridge
short nose with anteverted nostrils

Head And Neck Head:
prominent forehead

Head And Neck Eyes:
deep-set eyes

Growth Height:
short stature (if untreated)

Growth Other:
severe growth retardation in infancy

Skeletal Skull:
open sutures (untreated hypothyroidism)
open fontanelles (untreated hypothyroidism)

Neurologic Central Nervous System:
hypoplasia of anterior or entire pituitary gland (frequent)
mental retardation (untreated hypothyroidism)

Endocrine Features:
hypothyroidism

Head And Neck Face:
midface hypoplasia

Skin Nails Hair Skin:
jaundice, neonatal
myxedema (untreated hypothyroidism)

Laboratory Abnormalities:
low or absent growth hormone (gh)
low or absent thyroid-stimulating hormone (tsh)
low or absent prolactin (pl)

Head And Neck Mouth:
macroglossia (untreated hypothyroidism)

Muscle Soft Tissue:
hypotonia (untreated hypothyroidism)

Clinical features from OMIM:

613038

Drugs & Therapeutics for Pituitary Hormone Deficiency, Combined, 1

Search Clinical Trials , NIH Clinical Center for Pituitary Hormone Deficiency, Combined, 1

Genetic Tests for Pituitary Hormone Deficiency, Combined, 1

Genetic tests related to Pituitary Hormone Deficiency, Combined, 1:

# Genetic test Affiliating Genes
1 Pituitary Hormone Deficiency, Combined, 1 29 POU1F1

Anatomical Context for Pituitary Hormone Deficiency, Combined, 1

MalaCards organs/tissues related to Pituitary Hormone Deficiency, Combined, 1:

40
Pituitary, Eye, Thyroid

Publications for Pituitary Hormone Deficiency, Combined, 1

Articles related to Pituitary Hormone Deficiency, Combined, 1:

(show all 30)
# Title Authors PMID Year
1
Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency. 6 56
16968807 2006
2
Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency. 56 6
15928241 2005
3
A novel nonsense mutation in the Pit-1 gene: evidence for a gene dosage effect. 6 56
12629113 2003
4
Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene. 6 56
11297581 2001
5
Combined pituitary hormone deficiency due to the F135C human Pit-1 (pituitary-specific factor 1) gene mutation: functional and structural correlates. 6 56
11222742 2001
6
Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle Eastern children with growth hormone, prolactin, and thyrotropin deficiency. 6 56
9626142 1998
7
Pituitary dwarfism in the R271W Pit-1 gene mutation. 6 56
9392392 1997
8
A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency. 6 56
8768831 1996
9
A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency. 6 56
7670563 1995
10
Monoallelic expression of normal mRNA in the PIT1 mutation heterozygotes with normal phenotype and biallelic expression in the abnormal phenotype. 6 56
7833912 1994
11
Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency. 6 56
1472057 1992
12
A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. 56 6
1509262 1992
13
Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. 56 6
1509263 1992
14
Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene. 56 6
1302000 1992
15
Total deficiency of growth hormone and prolactin, and partial deficiency of thyroid stimulating hormone in two Dutch families: a new variant of hereditary pituitary deficiency. 6 56
2634610 1989
16
Congenital hypothyroidism in a young man with growth hormone, thyrotropin, and prolactin deficiencies. 56 6
1271194 1976
17
Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter? 56
16060904 2005
18
A novel mutation in PIT-1: phenotypic variability in familial combined pituitary hormone deficiencies. 6
11924936 2002
19
Molecular analysis of LHX3 and PROP-1 in pituitary hormone deficiency patients with posterior pituitary ectopia. 56
10946868 2000
20
"Hot spot" in the PROP1 gene responsible for combined pituitary hormone deficiency. 6
10323394 1999
21
The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. 6
9745452 1998
22
Description of a Brazilian patient bearing the R271W Pit-1 gene mutation. 6
9588494 1998
23
Mutations in PROP1 cause familial combined pituitary hormone deficiency. 56
9462743 1998
24
The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency. 56
7593413 1995
25
A novel pituitary transcription factor is produced by alternative splicing of the human GHF-1/PIT-1 gene. 6
7721104 1995
26
Anterior pituitary development: short tales from dwarf mice. 56
1505020 1992
27
The natural history of familial hypopituitarism. 56
2998186 1985
28
General Tom Thumb and other midgets. 56
6046325 1967
29
[Clinical and genetic characteristics of a young child with combined pituitary hormone deficiency type I caused by POU1F1 gene variation]. 61
31315769 2019
30
Genetic analysis of nitric oxide and endothelin in end-stage renal disease. 61
11071967 2000

Variations for Pituitary Hormone Deficiency, Combined, 1

ClinVar genetic disease variations for Pituitary Hormone Deficiency, Combined, 1:

6 (show all 49) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 HESX1 NM_003865.3(HESX1):c.313T>G (p.Trp105Gly)SNV Pathogenic 492850 rs754137696 3:57232825-57232825 3:57198797-57198797
2 HESX1 NM_003865.3(HESX1):c.240del (p.Glu81fs)deletion Pathogenic 492848 rs777833871 3:57232898-57232898 3:57198870-57198870
3 POU1F1 NM_000306.4(POU1F1):c.472G>C (p.Ala158Pro)SNV Pathogenic 13604 rs104893756 3:87311353-87311353 3:87262203-87262203
4 POU1F1 NM_000306.4(POU1F1):c.71C>T (p.Pro24Leu)SNV Pathogenic 13605 rs104893757 3:87325542-87325542 3:87276392-87276392
5 POU1F1 NM_000306.4(POU1F1):c.428G>A (p.Arg143Gln)SNV Pathogenic 13606 rs104893759 3:87313449-87313449 3:87264299-87264299
6 POU1F1 NM_000306.4(POU1F1):c.748G>T (p.Glu250Ter)SNV Pathogenic 13607 rs104893760 3:87309172-87309172 3:87260022-87260022
7 POU1F1 NM_000306.4(POU1F1):c.404T>G (p.Phe135Cys)SNV Pathogenic 13608 rs104893761 3:87313473-87313473 3:87264323-87264323
8 POU1F1 NM_000306.4(POU1F1):c.715C>T (p.Pro239Ser)SNV Pathogenic 13609 rs104893762 3:87309205-87309205 3:87260055-87260055
9 POU1F1 NM_000306.4(POU1F1):c.747del (p.Glu250fs)deletion Pathogenic 13610 rs587776798 3:87309173-87309173 3:87260023-87260023
10 POU1F1 NM_000306.4(POU1F1):c.577T>C (p.Trp193Arg)SNV Pathogenic 13611 rs104893758 3:87311248-87311248 3:87262098-87262098
11 POU1F1 NM_000306.4(POU1F1):c.433A>T (p.Lys145Ter)SNV Pathogenic 13612 rs104893763 3:87313444-87313444 3:87264294-87264294
12 POU1F1 NM_000306.4(POU1F1):c.688G>A (p.Glu230Lys)SNV Pathogenic 13613 rs104893764 3:87309232-87309232 3:87260082-87260082
13 POU1F1 NM_000306.4(POU1F1):c.775dup (p.Arg259fs)duplication Pathogenic 13615 rs587776799 3:87309144-87309145 3:87259994-87259995
14 POU1F1 NM_000306.4(POU1F1):c.537C>G (p.Ser179Arg)SNV Pathogenic 13616 rs104893766 3:87311288-87311288 3:87262138-87262138
15 POU1F1 NM_000306.4(POU1F1):c.665+1G>TSNV Pathogenic 126542 rs515726221 3:87310422-87310422 3:87261272-87261272
16 POU1F1 NM_000306.4(POU1F1):c.514C>T (p.Arg172Ter)SNV Pathogenic 13602 rs104893754 3:87311311-87311311 3:87262161-87262161
17 POU1F1 NM_000306.4(POU1F1):c.638_642del (p.Arg213fs)deletion Likely pathogenic 254175 rs772390221 3:87310446-87310450 3:87261296-87261300
18 POU1F1 NM_000306.4(POU1F1):c.215-3C>GSNV Likely pathogenic 254176 rs754584667 3:87313665-87313665 3:87264515-87264515
19 POU1F1 NC_000003.12:g.87310484C>TSNV Likely pathogenic 161432 rs606231411 3:87359634-87359634 3:87310484-87310484
20 POU1F1 NM_000306.4(POU1F1):c.515G>A (p.Arg172Gln)SNV Likely pathogenic 13614 rs104893765 3:87311310-87311310 3:87262160-87262160
21 HESX1 NM_003865.3(HESX1):c.308T>A (p.Leu103Ter)SNV Likely pathogenic 492849 rs777223697 3:57232830-57232830 3:57198802-57198802
22 POU1F1 NM_000306.4(POU1F1):c.439+4T>CSNV Conflicting interpretations of pathogenicity 513086 rs199746697 3:87313434-87313434 3:87264284-87264284
23 POU1F1 NM_000306.4(POU1F1):c.252C>T (p.His84=)SNV Conflicting interpretations of pathogenicity 597988 rs4988460 3:87313625-87313625 3:87264475-87264475
24 HESX1 NM_003865.3(HESX1):c.385G>A (p.Val129Ile)SNV Conflicting interpretations of pathogenicity 267733 rs143057250 3:57232493-57232493 3:57198465-57198465
25 POU1F1 NM_000306.4(POU1F1):c.370A>G (p.Met124Val)SNV Conflicting interpretations of pathogenicity 346844 rs143373007 3:87313507-87313507 3:87264357-87264357
26 POU1F1 NM_000306.4(POU1F1):c.*245A>GSNV Uncertain significance 346828 rs771316195 3:87308799-87308799 3:87259649-87259649
27 POU1F1 NM_000306.4(POU1F1):c.427C>A (p.Arg143=)SNV Uncertain significance 346843 rs142046308 3:87313450-87313450 3:87264300-87264300
28 POU1F1 NM_000306.4(POU1F1):c.-48T>CSNV Uncertain significance 346847 rs771498395 3:87325660-87325660 3:87276510-87276510
29 POU1F1 NM_000306.4(POU1F1):c.-105T>CSNV Uncertain significance 346848 rs886058915 3:87325717-87325717 3:87276567-87276567
30 POU1F1 NM_000306.4(POU1F1):c.456T>C (p.Asn152=)SNV Uncertain significance 346842 rs886058914 3:87311369-87311369 3:87262219-87262219
31 POU1F1 NM_000306.4(POU1F1):c.90T>A (p.Ser30Arg)SNV Uncertain significance 346846 rs543096490 3:87325523-87325523 3:87276373-87276373
32 POU1F1 NM_000306.4(POU1F1):c.*141A>TSNV Uncertain significance 346832 rs552876873 3:87308903-87308903 3:87259753-87259753
33 POU1F1 NM_000306.4(POU1F1):c.667A>G (p.Ile223Val)SNV Uncertain significance 346838 rs770960302 3:87309253-87309253 3:87260103-87260103
34 POU1F1 NM_000306.4(POU1F1):c.604+9T>CSNV Uncertain significance 346841 rs374875206 3:87311212-87311212 3:87262062-87262062
35 LHX3 NM_178138.6(LHX3):c.281A>T (p.Gln94Leu)SNV Uncertain significance 492770 rs758634719 9:139091697-139091697 9:136199851-136199851
36 POU1F1 NM_000306.4(POU1F1):c.811C>T (p.Arg271Trp)SNV Uncertain significance 13603 rs104893755 3:87309109-87309109 3:87259959-87259959
37 POU1F1 NM_000306.4(POU1F1):c.486C>T (p.Gly162=)SNV Uncertain significance 900533 3:87311339-87311339 3:87262189-87262189
38 POU1F1 NM_000306.4(POU1F1):c.27T>C (p.Ala9=)SNV Uncertain significance 902196 3:87325586-87325586 3:87276436-87276436
39 POU1F1 NM_000306.4(POU1F1):c.439+12T>CSNV Uncertain significance 900534 3:87313426-87313426 3:87264276-87264276
40 HESX1 NM_003865.3(HESX1):c.200G>A (p.Ser67Asn)SNV Uncertain significance 492847 rs141863326 3:57232938-57232938 3:57198910-57198910
41 LHX4 NM_033343.4(LHX4):c.359G>A (p.Cys120Tyr)SNV Uncertain significance 492768 rs1553282666 1:180235637-180235637 1:180266502-180266502
42 LHX4 NM_033343.4(LHX4):c.740A>T (p.Glu247Val)SNV Uncertain significance 492769 rs766381404 1:180241103-180241103 1:180271968-180271968
43 LHX3 NM_178138.6(LHX3):c.309G>T (p.Val103=)SNV Likely benign 492771 rs766945737 9:139091669-139091669 9:136199823-136199823
44 CHMP2B , POU1F1 NM_000306.4(POU1F1):c.666-5G>ASNV Benign/Likely benign 198069 rs76296626 3:87309259-87309259 3:87260109-87260109
45 CHMP2B , POU1F1 NM_000306.4(POU1F1):c.*140A>TSNV Benign/Likely benign 346833 rs33936108 3:87308904-87308904 3:87259754-87259754
46 CHMP2B , POU1F1 NM_000306.4(POU1F1):c.*139T>ASNV Benign/Likely benign 346836 rs4988463 3:87308905-87308905 3:87259755-87259755
47 CHMP2B , POU1F1 NM_000306.4(POU1F1):c.*138T>ASNV Benign/Likely benign 346837 rs190287993 3:87308906-87308906 3:87259756-87259756
48 CHMP2B , POU1F1 NM_000306.4(POU1F1):c.*213=SNV Benign 346829 rs6792500 3:87308831-87308831 3:87259681-87259681
49 POU1F1 NM_000306.4(POU1F1):c.40C>G (p.Pro14Ala)SNV not provided 585096 rs200873915 3:87325573-87325573 3:87276423-87276423

UniProtKB/Swiss-Prot genetic disease variations for Pituitary Hormone Deficiency, Combined, 1:

73 (show all 13)
# Symbol AA change Variation ID SNP ID
1 POU1F1 p.Pro24Leu VAR_003777 rs104893757
2 POU1F1 p.Arg143Gln VAR_003778 rs104893759
3 POU1F1 p.Ala158Pro VAR_003779 rs104893756
4 POU1F1 p.Arg271Trp VAR_003781 rs104893755
5 POU1F1 p.Phe135Cys VAR_010574 rs104893761
6 POU1F1 p.Glu174Gly VAR_010575 rs120717916
7 POU1F1 p.Pro239Ser VAR_010576 rs104893762
8 POU1F1 p.Trp193Arg VAR_015260 rs104893758
9 POU1F1 p.Arg172Gln VAR_063425 rs104893765
10 POU1F1 p.Ser179Arg VAR_063426 rs104893766
11 POU1F1 p.Glu230Lys VAR_063427 rs104893764
12 POU1F1 p.Pro76Leu VAR_075530
13 POU1F1 p.Arg265Trp VAR_075531 rs780359925

Expression for Pituitary Hormone Deficiency, Combined, 1

Search GEO for disease gene expression data for Pituitary Hormone Deficiency, Combined, 1.

Pathways for Pituitary Hormone Deficiency, Combined, 1

GO Terms for Pituitary Hormone Deficiency, Combined, 1

Cellular components related to Pituitary Hormone Deficiency, Combined, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclear chromatin GO:0000790 8.92 POU1F1 LHX4 LHX3 HESX1

Biological processes related to Pituitary Hormone Deficiency, Combined, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of transcription, DNA-templated GO:0006355 9.67 POU1F1 LHX4 LHX3 HESX1
2 placenta development GO:0001890 9.32 LHX4 LHX3
3 motor neuron axon guidance GO:0008045 9.26 LHX4 LHX3
4 acyl-CoA metabolic process GO:0006637 9.16 LHX4-AS1 ACBD6
5 medial motor column neuron differentiation GO:0021526 8.96 LHX4 LHX3
6 pituitary gland development GO:0021983 8.8 POU1F1 LHX3 HESX1

Molecular functions related to Pituitary Hormone Deficiency, Combined, 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.54 POU1F1 LHX3 HESX1
2 DNA-binding transcription activator activity, RNA polymerase II-specific GO:0001228 9.5 POU1F1 LHX4 LHX3
3 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.46 POU1F1 LHX4 LHX3 HESX1
4 RNA polymerase II transcription factor binding GO:0001085 9.26 POU1F1 LHX3
5 sequence-specific DNA binding GO:0043565 9.26 POU1F1 LHX4 LHX3 HESX1
6 fatty-acyl-CoA binding GO:0000062 8.62 LHX4-AS1 ACBD6

Sources for Pituitary Hormone Deficiency, Combined, 1

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