MCID: PSD117
MIFTS: 36

Pseudohypoparathyroidism, Type Ic

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

Aliases & Classifications for Pseudohypoparathyroidism, Type Ic

MalaCards integrated aliases for Pseudohypoparathyroidism, Type Ic:

Name: Pseudohypoparathyroidism, Type Ic 57 40
Pseudohypoparathyroidism Type 1c 53 59 29 6 73
Php1c 57 53 75
Pseudohypoparathyroidism Ic 57 13
Pseudohypoparathyroidism 1c 75
Php Ic 57

Characteristics:

Orphanet epidemiological data:

59
pseudohypoparathyroidism type 1c
Inheritance: Autosomal dominant; Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
autosomal dominant

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


HPO:

32
pseudohypoparathyroidism, type ic:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Pseudohypoparathyroidism, Type Ic

NIH Rare Diseases : 53 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 body mass index quantitative trait locus 11, 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, skin and eye, and related phenotypes are short neck and obesity

OMIM : 57 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 : 75 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 10.1
2 body mass index quantitative trait locus 11 9.0 GNAS MC4R

Symptoms & Phenotypes for Pseudohypoparathyroidism, Type Ic

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Neck:
short neck

Head And Neck Eyes:
nystagmus
cataract

Neurologic Central Nervous System:
seizures
hypocalcemic tetany
mental retardation
cognitive deficits
basal ganglion calcification
more
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

Growth Weight:
obesity

Endocrine Features:
hypothyroidism
hypogonadism
pseudohypoparathyroidism

Growth Height:
short stature

Head And Neck Face:
full cheeks
round face

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

Human phenotypes related to Pseudohypoparathyroidism, Type Ic:

59 32 (show top 50) (show all 60)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short neck 59 32 frequent (33%) Frequent (79-30%) HP:0000470
2 obesity 59 32 frequent (33%) Frequent (79-30%) HP:0001513
3 nystagmus 59 32 frequent (33%) Frequent (79-30%) HP:0000639
4 depressivity 59 32 occasional (7.5%) Occasional (29-5%) HP:0000716
5 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
6 cataract 59 32 frequent (33%) Frequent (79-30%) HP:0000518
7 depressed nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0005280
8 short stature 59 32 frequent (33%) Frequent (79-30%) HP:0004322
9 dyspnea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002094
10 full cheeks 59 32 frequent (33%) Frequent (79-30%) HP:0000293
11 irritability 59 32 occasional (7.5%) Occasional (29-5%) HP:0000737
12 delayed eruption of teeth 59 32 frequent (33%) Frequent (79-30%) HP:0000684
13 anxiety 59 32 occasional (7.5%) Occasional (29-5%) HP:0000739
14 short 4th metacarpal 59 32 frequent (33%) Frequent (79-30%) HP:0010044
15 short 5th metacarpal 59 32 frequent (33%) Frequent (79-30%) HP:0010047
16 prolonged qt interval 59 32 occasional (7.5%) Occasional (29-5%) HP:0001657
17 paresthesia 59 32 occasional (7.5%) Occasional (29-5%) HP:0003401
18 hypergonadotropic hypogonadism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000815
19 muscle cramps 59 32 occasional (7.5%) Occasional (29-5%) HP:0003394
20 brachydactyly 59 32 frequent (33%) Frequent (79-30%) HP:0001156
21 round face 59 32 frequent (33%) Frequent (79-30%) HP:0000311
22 chest pain 59 32 occasional (7.5%) Occasional (29-5%) HP:0100749
23 elevated circulating parathyroid hormone level 59 32 hallmark (90%) Very frequent (99-80%) HP:0003165
24 conjunctivitis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000509
25 increased bone mineral density 59 32 occasional (7.5%) Occasional (29-5%) HP:0011001
26 hyporeflexia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001265
27 polyphagia 59 32 frequent (33%) Frequent (79-30%) HP:0002591
28 short metacarpal 59 32 Frequent (79-30%) HP:0010049
29 pseudohypoparathyroidism 59 32 obligate (100%) Obligate (100%) HP:0000852
30 confusion 59 32 occasional (7.5%) Occasional (29-5%) HP:0001289
31 prolactin deficiency 59 32 very rare (1%) Very rare (<4-1%) HP:0008202
32 short metatarsal 59 32 Frequent (79-30%) HP:0010743
33 growth hormone deficiency 59 32 frequent (33%) Frequent (79-30%) HP:0000824
34 hypoplasia of dental enamel 59 32 frequent (33%) Frequent (79-30%) HP:0006297
35 hyperphosphatemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002905
36 hypocalcemic seizures 59 32 very rare (1%) Very rare (<4-1%) HP:0002199
37 short fifth metatarsal 59 32 frequent (33%) Frequent (79-30%) HP:0004704
38 oligomenorrhea 59 32 occasional (7.5%) Occasional (29-5%) HP:0000876
39 abdominal symptom 59 32 occasional (7.5%) Occasional (29-5%) HP:0011458
40 ectopic ossification 59 32 frequent (33%) Frequent (79-30%) HP:0011986
41 laryngeal dystonia 59 32 occasional (7.5%) Occasional (29-5%) HP:0012049
42 hypocalcemic tetany 59 32 occasional (7.5%) Occasional (29-5%) HP:0003472
43 low urinary cyclic amp response to pth administration 59 32 hallmark (90%) Very frequent (99-80%) HP:0003456
44 myoclonic spasms 59 32 occasional (7.5%) Occasional (29-5%) HP:0003739
45 calcinosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003761
46 basal ganglia calcification 59 32 frequent (33%) Frequent (79-30%) HP:0002135
47 pituitary resistance to thyroid hormone 59 32 hallmark (90%) Very frequent (99-80%) HP:0008227
48 choroid plexus calcification 59 32 frequent (33%) Frequent (79-30%) HP:0006960
49 constrictive median neuropathy 59 32 frequent (33%) Frequent (79-30%) HP:0012185
50 broad distal phalanx of the thumb 59 32 occasional (7.5%) Occasional (29-5%) HP:0009642

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:

41
Bone, Skin, Eye, Pituitary, Thyroid

Publications for Pseudohypoparathyroidism, Type Ic

Articles related to Pseudohypoparathyroidism, Type Ic:

# Title Authors Year
1
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. ( 24878042 )
2014
2
Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction. ( 21488135 )
2011
3
Resistance to epinephrine and hypersensitivity (hyperresponsiveness) to CB1 antagonists in a patient with pseudohypoparathyroidism type Ic. ( 20075145 )
2010

Variations for Pseudohypoparathyroidism, Type Ic

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

75
# Symbol AA change Variation ID SNP ID
1 GNAS p.Leu388Arg VAR_066387 rs397514457
2 GNAS p.Glu392Lys VAR_066388 rs397514456

ClinVar genetic disease variations for Pseudohypoparathyroidism, Type Ic:

6
(show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 GNAS GNAS, TYR391TER undetermined variant Pathogenic
2 GNAS NM_001077488.3(GNAS): c.1177G> T (p.Glu393Ter) single nucleotide variant Pathogenic rs397514456 GRCh37 Chromosome 20, 57485873: 57485873
3 GNAS NM_001077488.3(GNAS): c.1177G> T (p.Glu393Ter) single nucleotide variant Pathogenic rs397514456 GRCh38 Chromosome 20, 58910818: 58910818
4 GNAS NM_001077488.3(GNAS): c.1166T> G (p.Leu389Arg) single nucleotide variant Pathogenic rs397514457 GRCh37 Chromosome 20, 57485862: 57485862
5 GNAS NM_001077488.3(GNAS): c.1166T> G (p.Leu389Arg) single nucleotide variant Pathogenic rs397514457 GRCh38 Chromosome 20, 58910807: 58910807
6 GNAS NM_001077488.3(GNAS): c.1177G> A (p.Glu393Lys) single nucleotide variant Pathogenic rs397514456 GRCh37 Chromosome 20, 57485873: 57485873
7 GNAS NM_001077488.3(GNAS): c.1177G> A (p.Glu393Lys) single nucleotide variant Pathogenic rs397514456 GRCh38 Chromosome 20, 58910818: 58910818
8 GNAS NM_000516.5(GNAS): c.880C> T (p.Gln294Ter) single nucleotide variant Likely pathogenic rs863224876 GRCh37 Chromosome 20, 57485046: 57485046
9 GNAS NM_000516.5(GNAS): c.880C> T (p.Gln294Ter) single nucleotide variant Likely pathogenic rs863224876 GRCh38 Chromosome 20, 58909991: 58909991
10 GNAS NM_080425.3(GNAS): c.1200C> A (p.Ala400=) single nucleotide variant Uncertain significance rs908810796 GRCh37 Chromosome 20, 57429520: 57429520
11 GNAS NM_080425.3(GNAS): c.1200C> A (p.Ala400=) single nucleotide variant Uncertain significance rs908810796 GRCh38 Chromosome 20, 58854465: 58854465
12 GNAS NM_080425.3(GNAS): c.1455C> A (p.Ala485=) single nucleotide variant Uncertain significance rs55890501 GRCh37 Chromosome 20, 57429775: 57429775
13 GNAS NM_080425.3(GNAS): c.1455C> A (p.Ala485=) single nucleotide variant Uncertain significance rs55890501 GRCh38 Chromosome 20, 58854720: 58854720

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 GNAS MC4R

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 GNAS MC4R
2 adenylate cyclase-modulating G-protein coupled receptor signaling pathway GO:0007188 8.96 GNAS MC4R
3 energy reserve metabolic process GO:0006112 8.62 GNAS MC4R

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

# Name GO ID Score Top Affiliating Genes
1 obsolete signal transducer activity GO:0004871 8.62 GNAS MC4R

Sources for Pseudohypoparathyroidism, Type Ic

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
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30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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