PHP1C
MCID: PSD117
MIFTS: 38

Pseudohypoparathyroidism, Type Ic (PHP1C)

Categories: Blood diseases, Bone diseases, Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases, Skin diseases

Aliases & Classifications for Pseudohypoparathyroidism, Type Ic

MalaCards integrated aliases for Pseudohypoparathyroidism, Type Ic:

Name: Pseudohypoparathyroidism, Type Ic 56 39
Pseudohypoparathyroidism Type 1c 52 58 29 6 71
Php1c 56 52 73
Pseudohypoparathyroidism Ic 56 13
Pseudohypoparathyroidism 1c 73
Php Ic 56

Characteristics:

Orphanet epidemiological data:

58
pseudohypoparathyroidism type 1c
Inheritance: Autosomal dominant; Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
caused by inheritance of the mutation on the maternal allele (imprinting)
see also pseudohypoparathyroidism type ia


HPO:

31
pseudohypoparathyroidism, type ic:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare eye diseases
Rare renal diseases
Rare bone diseases
Rare skin diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Pseudohypoparathyroidism, Type Ic

NIH Rare Diseases : 52 Pseudohypoparathyroidism type 1C is a genetic disorder that is very similar to hypoparathyroidism (parathyroid hormone levels are too low). However, pseudohypoparathyroidism is caused by no response to parathyroid hormone rather than having too little of the hormone itself. This causes low calcium and high phosphate levels in the blood. This condition is also associated with a group of symptoms referred to as Albright's hereditary osteodystrophy , which includes short stature , a round face, obesity, and short hand bones. This disorder is different than pseudohypoparathyroidism type 1A because people with type 1C do not have abnormal activity of a particular protein (stimulatory protein G (Gs alpha)). Type 1C is inherited in an autosomal dominant fashion and is caused by a specific spelling mistake (mutation ) in the GNAS gene .

MalaCards based summary : Pseudohypoparathyroidism, Type Ic, also known as pseudohypoparathyroidism type 1c, is related to pseudohypoparathyroidism and pseudohypoparathyroidism, type ia, and has symptoms including seizures An important gene associated with Pseudohypoparathyroidism, Type Ic is GNAS (GNAS Complex Locus), and among its related pathways/superpathways is G alpha (s) signalling events. Affiliated tissues include bone, eye and thyroid, and related phenotypes are pseudohypoparathyroidism and hyperphosphatemia

OMIM : 56 Pseudohypoparathyroidism type Ic (PHP1C) is characterized by resistance to parathyroid hormone (PTH; 168450) as well as to other hormones. It is associated with a constellation of physical features referred to as Albright hereditary osteodystrophy (AHO), which includes short stature, obesity, round facies, subcutaneous ossifications, brachydactyly, and other skeletal anomalies. Some patients have mental retardation. Laboratory studies in patients with PHP Ic show a decreased cellular cyclic AMP (cAMP) response to infused PTH, but no defect in activity of the erythrocyte Gs protein (Mantovani and Spada, 2006). (612462)

UniProtKB/Swiss-Prot : 73 Pseudohypoparathyroidism 1C: A disorder characterized by end-organ resistance to parathyroid hormone, hypocalcemia and hyperphosphatemia. It is commonly associated with Albright hereditary osteodystrophy whose features are short stature, obesity, round facies, short metacarpals and ectopic calcification.

Related Diseases for Pseudohypoparathyroidism, Type Ic

Diseases in the Pseudohypoparathyroidism family:

Pseudohypoparathyroidism, Type Ia Pseudohypoparathyroidism, Type Ii
Pseudohypoparathyroidism, Type Ib Pseudohypoparathyroidism, Type Ic

Diseases related to Pseudohypoparathyroidism, Type Ic via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 pseudohypoparathyroidism 29.6 MC4R GNAS
2 pseudohypoparathyroidism, type ia 29.4 MC4R GNAS
3 leptin deficiency or dysfunction 10.0
4 allergic hypersensitivity disease 10.0
5 cholera 10.0
6 disorders of gnas inactivation 10.0
7 body mass index quantitative trait locus 11 9.2 MC4R GNAS

Graphical network of the top 20 diseases related to Pseudohypoparathyroidism, Type Ic:



Diseases related to Pseudohypoparathyroidism, Type Ic

Symptoms & Phenotypes for Pseudohypoparathyroidism, Type Ic

Human phenotypes related to Pseudohypoparathyroidism, Type Ic:

58 31 (show top 50) (show all 61)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pseudohypoparathyroidism 58 31 obligate (100%) Obligate (100%) HP:0000852
2 hyperphosphatemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002905
3 elevated circulating parathyroid hormone level 58 31 hallmark (90%) Very frequent (99-80%) HP:0003165
4 low urinary cyclic amp response to pth administration 58 31 hallmark (90%) Very frequent (99-80%) HP:0003456
5 pituitary resistance to thyroid hormone 58 31 hallmark (90%) Very frequent (99-80%) HP:0008227
6 cataract 58 31 frequent (33%) Frequent (79-30%) HP:0000518
7 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
8 depressed nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0005280
9 short neck 58 31 frequent (33%) Frequent (79-30%) HP:0000470
10 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
11 full cheeks 58 31 frequent (33%) Frequent (79-30%) HP:0000293
12 nystagmus 58 31 frequent (33%) Frequent (79-30%) HP:0000639
13 obesity 58 31 frequent (33%) Frequent (79-30%) HP:0001513
14 short 4th metacarpal 58 31 frequent (33%) Frequent (79-30%) HP:0010044
15 short 5th metacarpal 58 31 frequent (33%) Frequent (79-30%) HP:0010047
16 delayed eruption of teeth 58 31 frequent (33%) Frequent (79-30%) HP:0000684
17 brachydactyly 58 31 frequent (33%) Frequent (79-30%) HP:0001156
18 round face 58 31 frequent (33%) Frequent (79-30%) HP:0000311
19 constrictive median neuropathy 58 31 frequent (33%) Frequent (79-30%) HP:0012185
20 growth hormone deficiency 58 31 frequent (33%) Frequent (79-30%) HP:0000824
21 hypoplasia of dental enamel 58 31 frequent (33%) Frequent (79-30%) HP:0006297
22 polyphagia 58 31 frequent (33%) Frequent (79-30%) HP:0002591
23 short fifth metatarsal 58 31 frequent (33%) Frequent (79-30%) HP:0004704
24 ectopic ossification 58 31 frequent (33%) Frequent (79-30%) HP:0011986
25 basal ganglia calcification 58 31 frequent (33%) Frequent (79-30%) HP:0002135
26 choroid plexus calcification 58 31 frequent (33%) Frequent (79-30%) HP:0006960
27 dyspnea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002094
28 irritability 58 31 occasional (7.5%) Occasional (29-5%) HP:0000737
29 chest pain 58 31 occasional (7.5%) Occasional (29-5%) HP:0100749
30 anxiety 58 31 occasional (7.5%) Occasional (29-5%) HP:0000739
31 depressivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0000716
32 prolonged qt interval 58 31 occasional (7.5%) Occasional (29-5%) HP:0001657
33 paresthesia 58 31 occasional (7.5%) Occasional (29-5%) HP:0003401
34 increased bone mineral density 58 31 occasional (7.5%) Occasional (29-5%) HP:0011001
35 conjunctivitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000509
36 hyporeflexia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001265
37 hypergonadotropic hypogonadism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000815
38 muscle spasm 58 31 occasional (7.5%) Occasional (29-5%) HP:0003394
39 confusion 58 31 occasional (7.5%) Occasional (29-5%) HP:0001289
40 calcinosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0003761
41 hypocalcemic tetany 58 31 occasional (7.5%) Occasional (29-5%) HP:0003472
42 myoclonic spasms 58 31 occasional (7.5%) Occasional (29-5%) HP:0003739
43 oligomenorrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0000876
44 abdominal symptom 58 31 occasional (7.5%) Occasional (29-5%) HP:0011458
45 laryngeal dystonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0012049
46 broad distal phalanx of the thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0009642
47 short 3rd metacarpal 58 31 occasional (7.5%) Occasional (29-5%) HP:0010041
48 osteoma cutis 58 31 occasional (7.5%) Occasional (29-5%) HP:0025027
49 hypocalcemic seizures 58 31 very rare (1%) Very rare (<4-1%) HP:0002199
50 reduced circulating prolactin concentration 31 very rare (1%) HP:0008202

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
cataract
nystagmus

Neurologic Central Nervous System:
seizures
hypocalcemic tetany
mental retardation
cognitive deficits
basal ganglion calcification
more
Endocrine Features:
hypothyroidism
pseudohypoparathyroidism
hypogonadism

Skeletal:
osteoporosis

Skeletal Hands:
brachydactyly
short metacarpals (especially 4th and 5th)

Laboratory Abnormalities:
hypocalcemia
hyperphosphatemia
low urinary cyclic amp response to pth administration
elevated serum parathyroid hormone (pth) level
normal erythrocyte gs activity

Head And Neck Nose:
low nasal bridge

Skin Nails Hair Skin:
subcutaneous ossifications

Head And Neck Neck:
short neck

Growth Height:
short stature

Head And Neck Face:
full cheeks
round face

Growth Weight:
obesity

Skeletal Feet:
brachydactyly
short metatarsals (especially 4th and 5th)

Neurologic Peripheral Nervous System:
hypocalcemic tetany

Head And Neck Teeth:
delayed tooth eruption
enamel hypoplasia

Clinical features from OMIM:

612462

UMLS symptoms related to Pseudohypoparathyroidism, Type Ic:


seizures

GenomeRNAi Phenotypes related to Pseudohypoparathyroidism, Type Ic according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Negative genetic interaction between PTTG1-/- and PTTG1+/+ GR00255-A-4 8.62 GNAS MC4R

Drugs & Therapeutics for Pseudohypoparathyroidism, Type Ic

Search Clinical Trials , NIH Clinical Center for Pseudohypoparathyroidism, Type Ic

Genetic Tests for Pseudohypoparathyroidism, Type Ic

Genetic tests related to Pseudohypoparathyroidism, Type Ic:

# Genetic test Affiliating Genes
1 Pseudohypoparathyroidism Type 1c 29 GNAS

Anatomical Context for Pseudohypoparathyroidism, Type Ic

MalaCards organs/tissues related to Pseudohypoparathyroidism, Type Ic:

40
Bone, Eye, Thyroid, Skin, Pituitary

Publications for Pseudohypoparathyroidism, Type Ic

Articles related to Pseudohypoparathyroidism, Type Ic:

# Title Authors PMID Year
1
Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsα-receptor interaction. 61 56 6
21488135 2011
2
GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance. 6 56
11788646 2002
3
Disorders of GNAS Inactivation 6
29072892 2017
4
The GNAS locus and pseudohypoparathyroidism. 56
18372789 2008
5
Mutations in the Gs alpha gene causing hormone resistance. 56
17161328 2006
6
Pseudohypoparathyroidism: inheritance of deficient receptor-cyclase coupling activity. 56
6265935 1981
7
Different pattern of epigenetic changes of the GNAS gene locus in patients with pseudohypoparathyroidism type Ic confirm the heterogeneity of underlying pathomechanisms in this subgroup of pseudohypoparathyroidism and the demand for a new classification of GNAS-related disorders. 61
24878042 2014
8
Resistance to epinephrine and hypersensitivity (hyperresponsiveness) to CB1 antagonists in a patient with pseudohypoparathyroidism type Ic. 61
20075145 2010
9
[Cutaneous osteoma and Albright's hereditary osteodystrophy]. 61
7702269 1994

Variations for Pseudohypoparathyroidism, Type Ic

ClinVar genetic disease variations for Pseudohypoparathyroidism, Type Ic:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 GNAS GNAS, TYR391TERundetermined variant Pathogenic 15959
2 GNAS NM_001077488.4(GNAS):c.1177G>T (p.Glu393Ter)SNV Pathogenic 29745 rs397514456 20:57485873-57485873 20:58910818-58910818
3 GNAS NM_001077488.4(GNAS):c.1166T>G (p.Leu389Arg)SNV Pathogenic 29746 rs397514457 20:57485862-57485862 20:58910807-58910807
4 GNAS NM_001077488.4(GNAS):c.1177G>A (p.Glu393Lys)SNV Pathogenic 29747 rs397514456 20:57485873-57485873 20:58910818-58910818
5 GNAS NM_001077488.4(GNAS):c.85C>T (p.Gln29Ter)SNV Pathogenic 374113 rs1057518907 20:57466866-57466866 20:58891811-58891811
6 GNAS NM_001077488.4(GNAS):c.1A>G (p.Met1Val)SNV Pathogenic/Likely pathogenic 15927 rs137854530 20:57466782-57466782 20:58891727-58891727
7 GNAS NM_001077488.4(GNAS):c.883C>T (p.Gln295Ter)SNV Likely pathogenic 216937 rs863224876 20:57485046-57485046 20:58909991-58909991
8 GNAS NM_080425.3(GNAS):c.1200C>A (p.Ala400=)SNV Uncertain significance 417934 rs908810796 20:57429520-57429520 20:58854465-58854465
9 GNAS NM_080425.3(GNAS):c.1455C>A (p.Ala485=)SNV Benign 417936 rs55890501 20:57429775-57429775 20:58854720-58854720

UniProtKB/Swiss-Prot genetic disease variations for Pseudohypoparathyroidism, Type Ic:

73
# Symbol AA change Variation ID SNP ID
1 GNAS p.Leu388Arg VAR_066387 rs397514457
2 GNAS p.Glu392Lys VAR_066388 rs397514456

Expression for Pseudohypoparathyroidism, Type Ic

Search GEO for disease gene expression data for Pseudohypoparathyroidism, Type Ic.

Pathways for Pseudohypoparathyroidism, Type Ic

Pathways related to Pseudohypoparathyroidism, Type Ic according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.79 MC4R GNAS

GO Terms for Pseudohypoparathyroidism, Type Ic

Biological processes related to Pseudohypoparathyroidism, Type Ic according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 adenylate cyclase-activating G protein-coupled receptor signaling pathway GO:0007189 9.16 MC4R GNAS
2 adenylate cyclase-modulating G protein-coupled receptor signaling pathway GO:0007188 8.96 MC4R GNAS
3 energy reserve metabolic process GO:0006112 8.62 MC4R GNAS

Sources for Pseudohypoparathyroidism, Type Ic

3 CDC
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10 dbSNP
11 DGIdb
17 EFO
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57 OMIM via Orphanet
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63 QIAGEN
68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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