MCID: PTT045
MIFTS: 33

Pituitary Hormone Deficiency, Combined, 1

Categories: Genetic diseases, Rare diseases, Endocrine diseases

Aliases & Classifications for Pituitary Hormone Deficiency, Combined, 1

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

Name: Pituitary Hormone Deficiency, Combined, 1 57 75 13 73
Pituitary Hormone Deficiency, Combined 1 53 29 6
Cphd1 57 53 75
Hormone Deficiency, Pituitary, Combined, Type 1 40

Characteristics:

OMIM:

57
Inheritance:
autosomal recessive
autosomal dominant


HPO:

32
pituitary hormone deficiency, combined, 1:
Inheritance autosomal recessive inheritance autosomal dominant inheritance


Classifications:



Summaries for Pituitary Hormone Deficiency, Combined, 1

OMIM : 57 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 pituitary hormone deficiency, combined 1, is related to isolated growth hormone deficiency, type ii and septooptic dysplasia. 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 delayed cranial suture closure

UniProtKB/Swiss-Prot : 75 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

Symptoms via clinical synopsis from OMIM:

57
Endocrine Features:
hypothyroidism

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)

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

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

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

32 (show all 18)
# Description HPO Frequency HPO Source Accession
1 macroglossia 32 HP:0000158
2 delayed cranial suture closure 32 HP:0000270
3 malar flattening 32 HP:0000272
4 anteverted nares 32 HP:0000463
5 deeply set eye 32 HP:0000490
6 hypothyroidism 32 HP:0000821
7 jaundice 32 HP:0000952
8 intellectual disability 32 HP:0001249
9 muscular hypotonia 32 HP:0001252
10 generalized hypotonia 32 HP:0001290
11 frontal bossing 32 HP:0002007
12 short nose 32 HP:0003196
13 short stature 32 HP:0004322
14 depressed nasal bridge 32 HP:0005280
15 prolonged neonatal jaundice 32 HP:0006579
16 severe postnatal growth retardation 32 HP:0008850
17 prominent forehead 32 HP:0011220
18 midface retrusion 32 HP:0011800

MGI Mouse Phenotypes related to Pituitary Hormone Deficiency, Combined, 1:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.8 HESX1 LHX3 POU1F1

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:

41
Pituitary, Eye, Thyroid

Publications for Pituitary Hormone Deficiency, Combined, 1

Variations for Pituitary Hormone Deficiency, Combined, 1

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

75 (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
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

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

6
(show top 50) (show all 53)
# Gene Variation Type Significance SNP ID Assembly Location
1 POU1F1 NM_001122757.2(POU1F1): c.592C> T (p.Arg198Ter) single nucleotide variant Pathogenic rs104893754 GRCh37 Chromosome 3, 87311311: 87311311
2 POU1F1 NM_001122757.2(POU1F1): c.592C> T (p.Arg198Ter) single nucleotide variant Pathogenic rs104893754 GRCh38 Chromosome 3, 87262161: 87262161
3 POU1F1 NM_001122757.2(POU1F1): c.550G> C (p.Ala184Pro) single nucleotide variant Pathogenic rs104893756 GRCh37 Chromosome 3, 87311353: 87311353
4 POU1F1 NM_001122757.2(POU1F1): c.550G> C (p.Ala184Pro) single nucleotide variant Pathogenic rs104893756 GRCh38 Chromosome 3, 87262203: 87262203
5 POU1F1 NM_001122757.2(POU1F1): c.71C> T (p.Pro24Leu) single nucleotide variant Pathogenic rs104893757 GRCh37 Chromosome 3, 87325542: 87325542
6 POU1F1 NM_001122757.2(POU1F1): c.71C> T (p.Pro24Leu) single nucleotide variant Pathogenic rs104893757 GRCh38 Chromosome 3, 87276392: 87276392
7 POU1F1 NM_001122757.2(POU1F1): c.506G> A (p.Arg169Gln) single nucleotide variant Pathogenic rs104893759 GRCh37 Chromosome 3, 87313449: 87313449
8 POU1F1 NM_001122757.2(POU1F1): c.506G> A (p.Arg169Gln) single nucleotide variant Pathogenic rs104893759 GRCh38 Chromosome 3, 87264299: 87264299
9 POU1F1 NM_001122757.2(POU1F1): c.826G> T (p.Glu276Ter) single nucleotide variant Pathogenic rs104893760 GRCh37 Chromosome 3, 87309172: 87309172
10 POU1F1 NM_001122757.2(POU1F1): c.826G> T (p.Glu276Ter) single nucleotide variant Pathogenic rs104893760 GRCh38 Chromosome 3, 87260022: 87260022
11 POU1F1 NM_001122757.2(POU1F1): c.482T> G (p.Phe161Cys) single nucleotide variant Pathogenic rs104893761 GRCh37 Chromosome 3, 87313473: 87313473
12 POU1F1 NM_001122757.2(POU1F1): c.482T> G (p.Phe161Cys) single nucleotide variant Pathogenic rs104893761 GRCh38 Chromosome 3, 87264323: 87264323
13 POU1F1 NM_001122757.2(POU1F1): c.793C> T (p.Pro265Ser) single nucleotide variant Pathogenic rs104893762 GRCh37 Chromosome 3, 87309205: 87309205
14 POU1F1 NM_001122757.2(POU1F1): c.793C> T (p.Pro265Ser) single nucleotide variant Pathogenic rs104893762 GRCh38 Chromosome 3, 87260055: 87260055
15 POU1F1 NM_001122757.2(POU1F1): c.825delA (p.Glu276Asnfs) deletion Pathogenic rs587776798 GRCh37 Chromosome 3, 87309173: 87309173
16 POU1F1 NM_001122757.2(POU1F1): c.825delA (p.Glu276Asnfs) deletion Pathogenic rs587776798 GRCh38 Chromosome 3, 87260023: 87260023
17 POU1F1 NM_001122757.2(POU1F1): c.655T> C (p.Trp219Arg) single nucleotide variant Pathogenic rs104893758 GRCh37 Chromosome 3, 87311248: 87311248
18 POU1F1 NM_001122757.2(POU1F1): c.655T> C (p.Trp219Arg) single nucleotide variant Pathogenic rs104893758 GRCh38 Chromosome 3, 87262098: 87262098
19 POU1F1 NM_001122757.2(POU1F1): c.511A> T (p.Lys171Ter) single nucleotide variant Pathogenic rs104893763 GRCh37 Chromosome 3, 87313444: 87313444
20 POU1F1 NM_001122757.2(POU1F1): c.511A> T (p.Lys171Ter) single nucleotide variant Pathogenic rs104893763 GRCh38 Chromosome 3, 87264294: 87264294
21 POU1F1 NM_001122757.2(POU1F1): c.766G> A (p.Glu256Lys) single nucleotide variant Pathogenic rs104893764 GRCh37 Chromosome 3, 87309232: 87309232
22 POU1F1 NM_001122757.2(POU1F1): c.766G> A (p.Glu256Lys) single nucleotide variant Pathogenic rs104893764 GRCh38 Chromosome 3, 87260082: 87260082
23 POU1F1 NM_000306.3(POU1F1): c.515G> A (p.Arg172Gln) single nucleotide variant Likely pathogenic rs104893765 GRCh37 Chromosome 3, 87311310: 87311310
24 POU1F1 NM_000306.3(POU1F1): c.515G> A (p.Arg172Gln) single nucleotide variant Likely pathogenic rs104893765 GRCh38 Chromosome 3, 87262160: 87262160
25 POU1F1 NM_001122757.2(POU1F1): c.853dupA (p.Arg285Lysfs) duplication Pathogenic rs587776799 GRCh37 Chromosome 3, 87309145: 87309145
26 POU1F1 NM_001122757.2(POU1F1): c.853dupA (p.Arg285Lysfs) duplication Pathogenic rs587776799 GRCh38 Chromosome 3, 87259995: 87259995
27 POU1F1 NM_001122757.2(POU1F1): c.615C> G (p.Ser205Arg) single nucleotide variant Pathogenic rs104893766 GRCh37 Chromosome 3, 87311288: 87311288
28 POU1F1 NM_001122757.2(POU1F1): c.615C> G (p.Ser205Arg) single nucleotide variant Pathogenic rs104893766 GRCh38 Chromosome 3, 87262138: 87262138
29 POU1F1 NM_001122757.2(POU1F1): c.743+1G> T single nucleotide variant Pathogenic rs515726221 GRCh38 Chromosome 3, 87261272: 87261272
30 POU1F1 NM_001122757.2(POU1F1): c.743+1G> T single nucleotide variant Pathogenic rs515726221 GRCh37 Chromosome 3, 87310422: 87310422
31 POU1F1 NC_000003.12: g.87310484C> T single nucleotide variant Likely pathogenic rs606231411 GRCh38 Chromosome 3, 87310484: 87310484
32 POU1F1 NM_001122757.2(POU1F1): c.712_716delGAAAG (p.Arg239Lysfs) deletion Pathogenic rs886037826 GRCh37 Chromosome 3, 87310450: 87310454
33 POU1F1 NM_001122757.2(POU1F1): c.712_716delGAAAG (p.Arg239Lysfs) deletion Pathogenic rs886037826 GRCh38 Chromosome 3, 87261300: 87261304
34 POU1F1 NM_001122757.2(POU1F1): c.293-3C> G single nucleotide variant Likely pathogenic rs754584667 GRCh37 Chromosome 3, 87313665: 87313665
35 POU1F1 NM_001122757.2(POU1F1): c.293-3C> G single nucleotide variant Likely pathogenic rs754584667 GRCh38 Chromosome 3, 87264515: 87264515
36 HESX1 NM_003865.2(HESX1): c.385G> A (p.Val129Ile) single nucleotide variant Uncertain significance rs143057250 GRCh37 Chromosome 3, 57232493: 57232493
37 HESX1 NM_003865.2(HESX1): c.385G> A (p.Val129Ile) single nucleotide variant Uncertain significance rs143057250 GRCh38 Chromosome 3, 57198465: 57198465
38 LHX4 NM_033343.3(LHX4): c.359G> A (p.Cys120Tyr) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 180266502: 180266502
39 LHX4 NM_033343.3(LHX4): c.359G> A (p.Cys120Tyr) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 180235637: 180235637
40 LHX4 NM_033343.3(LHX4): c.740A> T (p.Glu247Val) single nucleotide variant Uncertain significance rs766381404 GRCh38 Chromosome 1, 180271968: 180271968
41 LHX4 NM_033343.3(LHX4): c.740A> T (p.Glu247Val) single nucleotide variant Uncertain significance rs766381404 GRCh37 Chromosome 1, 180241103: 180241103
42 HESX1 NM_003865.2(HESX1): c.313T> G (p.Trp105Gly) single nucleotide variant Pathogenic rs754137696 GRCh38 Chromosome 3, 57198797: 57198797
43 HESX1 NM_003865.2(HESX1): c.313T> G (p.Trp105Gly) single nucleotide variant Pathogenic rs754137696 GRCh37 Chromosome 3, 57232825: 57232825
44 HESX1 NM_003865.2(HESX1): c.308T> A (p.Leu103Ter) single nucleotide variant Pathogenic/Likely pathogenic rs777223697 GRCh38 Chromosome 3, 57198802: 57198802
45 HESX1 NM_003865.2(HESX1): c.308T> A (p.Leu103Ter) single nucleotide variant Pathogenic/Likely pathogenic rs777223697 GRCh37 Chromosome 3, 57232830: 57232830
46 HESX1 NM_003865.2(HESX1): c.240delA (p.Glu81Lysfs) deletion Pathogenic rs777833871 GRCh38 Chromosome 3, 57198870: 57198870
47 HESX1 NM_003865.2(HESX1): c.240delA (p.Glu81Lysfs) deletion Pathogenic rs777833871 GRCh37 Chromosome 3, 57232898: 57232898
48 HESX1 NM_003865.2(HESX1): c.200G> A (p.Ser67Asn) single nucleotide variant Uncertain significance rs141863326 GRCh38 Chromosome 3, 57198910: 57198910
49 HESX1 NM_003865.2(HESX1): c.200G> A (p.Ser67Asn) single nucleotide variant Uncertain significance rs141863326 GRCh37 Chromosome 3, 57232938: 57232938
50 LHX3 NM_178138.5(LHX3): c.309G> T (p.Val103=) single nucleotide variant Likely benign rs766945737 GRCh38 Chromosome 9, 136199823: 136199823

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

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

# Name GO ID Score Top Affiliating Genes
1 transcription by RNA polymerase II GO:0006366 9.54 LHX3 LHX4 POU1F1
2 animal organ morphogenesis GO:0009887 9.4 LHX3 LHX4
3 placenta development GO:0001890 9.32 LHX3 LHX4
4 acyl-CoA metabolic process GO:0006637 9.26 ACBD6 LHX4-AS1
5 motor neuron axon guidance GO:0008045 9.16 LHX3 LHX4
6 medial motor column neuron differentiation GO:0021526 8.96 LHX3 LHX4
7 pituitary gland development GO:0021983 8.8 HESX1 LHX3 POU1F1

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 transcription factor activity, sequence-specific DNA binding GO:0000981 9.56 HESX1 LHX3 LHX4 POU1F1
2 RNA polymerase II proximal promoter sequence-specific DNA binding GO:0000978 9.33 HESX1 LHX3 POU1F1
3 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding GO:0001228 9.32 LHX3 LHX4
4 RNA polymerase II transcription factor binding GO:0001085 8.96 LHX3 POU1F1
5 sequence-specific DNA binding GO:0043565 8.92 HESX1 LHX3 LHX4 POU1F1

Sources for Pituitary Hormone Deficiency, Combined, 1

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69 SNOMED-CT via HPO
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72 Tocris
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74 UMLS via Orphanet
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