MCID: HYP599
MIFTS: 39

Hypoparathyroidism, Familial Isolated

Categories: Genetic diseases, Rare diseases, Endocrine diseases, Eye diseases

Aliases & Classifications for Hypoparathyroidism, Familial Isolated

MalaCards integrated aliases for Hypoparathyroidism, Familial Isolated:

Name: Hypoparathyroidism, Familial Isolated 53 71
Hypoparathyroidism, Autosomal Recessive 53 28 69
Hypoparathyroidism Familial Isolated 49 28 69
Fih 53 71
Familial Isolated Hypoparathyroidism Due to Impaired Pth Secretion 55
Hypoparathyroidism - Autosomal Dominant 69
Hypoparathyroidism, Autosomal Dominant 53
Autosomal Recessive Hypoparathyroidism 71
Autosomal Dominant Hypoparathyroidism 71
Familial Isolated Hypoparathyroidism 55

Characteristics:

Orphanet epidemiological data:

55
familial isolated hypoparathyroidism due to impaired pth secretion
Inheritance: Autosomal dominant,Autosomal recessive;
familial isolated hypoparathyroidism
Inheritance: Autosomal dominant,Autosomal recessive,X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

53
Inheritance:
autosomal dominant


HPO:

31
hypoparathyroidism, familial isolated:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Hypoparathyroidism, Familial Isolated

NIH Rare Diseases : 49 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 2238Disease definitionFamilial isolated hypoparathyroidism (FIH) is a rare heterogeneous group of metabolic disorders characterized by abnormal calcium metabolism due to deficient secretion of parathormone (PTH), without other endocrine disorders or developmental defects. It can occur at any age (from the newborn period to adulthood) but generally starts within the first decade of life. The clinical signs are mainly those of hypocalcemia: myopathy, muscular weakness, cramps, tetany, lenticular cataracts, teeth anomalies and short stature. Isolated hypoparathyroidism may be sporadic or familial, with autosomal dominant or recessive inheritance. FIH may be due to an activating mutation of the calcium-sensing receptor (CASR) gene. This is the most common cause of genetic hypoparathyroidism and is transmitted as an autosomal dominant trait. It represents 42% of isolated hypoparathyroidism cases. Thirteen mutations have been described in familial or sporadic cases. In three families, mutations in the PTH gene have been identified. This type of FIH is transmitted as an autosomal recessive or dominant trait. One family has been reported with a mutation in the gene encoding the glial cells missing homolog b (GCMB) transcription factor. In this case, transmission is autosomal recessive. Diagnosis is made when hypocalcemia, hyperphosphoremia, and low or undetectable PTH levels are observed. Management consists of symptomatic treatment with supplementary calcium and vitamin D.Visit the Orphanet disease page for more resources. Last updated: 2/17/2005

MalaCards based summary : Hypoparathyroidism, Familial Isolated, also known as hypoparathyroidism, autosomal recessive, is related to hypoparathyroidism and familial isolated hypoparathyroidism due to agenesis of parathyroid gland, and has symptoms including seizures, cerebral calcification and cataract. An important gene associated with Hypoparathyroidism, Familial Isolated is PTH (Parathyroid Hormone). Affiliated tissues include thymus and eye, and related phenotype is endocrine/exocrine gland.

OMIM : 53 Garfield and Karaplis (2001) reviewed the various causes and clinical forms of hypoparathyroidism. They noted that hypoparathyroidism is a clinical disorder characterized by hypocalcemia and hyperphosphatemia. It manifests when parathyroid hormone (PTH; 168450) secreted from the parathyroid glands is insufficient to maintain normal extracellular fluid calcium concentrations or, less commonly, when PTH is unable to function optimally in target tissues, despite adequate circulating levels. Congenital absence of the parathyroid and thymus glands (III and IV pharyngeal pouch syndrome, or DiGeorge syndrome, 188400) is usually a sporadic condition (Taitz et al., 1966). (146200)

UniProtKB/Swiss-Prot : 71 Hypoparathyroidism, familial isolated: A disorder characterized by hypocalcemia and hyperphosphatemia due to inadequate secretion of parathyroid hormone. Clinical features include seizures, tetany and cramps.

Related Diseases for Hypoparathyroidism, Familial Isolated

Graphical network of the top 20 diseases related to Hypoparathyroidism, Familial Isolated:



Diseases related to Hypoparathyroidism, Familial Isolated

Symptoms & Phenotypes for Hypoparathyroidism, Familial Isolated

Symptoms via clinical synopsis from OMIM:

53
Neuro:
seizures
chronic tetany

Lab:
hypocalcemia
hyperphosphatemia
no circulating antibodies to parathyroid hormone
undetectable or subnormal plasma immunoreactive pth

Radiology:
intracerebral calcification on ct scan

Endocrine:
hypoparathyroidism

Eyes:
cataracts


Clinical features from OMIM:

146200

Human phenotypes related to Hypoparathyroidism, Familial Isolated:

55 31 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 hallmark (90%) Very frequent (99-80%) HP:0001250
2 cerebral calcification 55 31 frequent (33%) Frequent (79-30%) HP:0002514
3 cataract 55 31 frequent (33%) Frequent (79-30%) HP:0000518
4 short stature 55 31 hallmark (90%) Very frequent (99-80%) HP:0004322
5 nephropathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0000112
6 myopathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0003198
7 arrhythmia 55 31 frequent (33%) Frequent (79-30%) HP:0011675
8 delayed eruption of teeth 55 31 frequent (33%) Frequent (79-30%) HP:0000684
9 hypoparathyroidism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000829
10 abnormality of dental enamel 55 31 frequent (33%) Frequent (79-30%) HP:0000682
11 hypocalcemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002901
12 abnormality of calcium-phosphate metabolism 55 31 hallmark (90%) Very frequent (99-80%) HP:0100530
13 tetany 31 HP:0001281
14 hyperphosphatemia 31 HP:0002905

MGI Mouse Phenotypes related to Hypoparathyroidism, Familial Isolated:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 8.8 AIRE GCM2 PTH

Drugs & Therapeutics for Hypoparathyroidism, Familial Isolated

Search Clinical Trials , NIH Clinical Center for Hypoparathyroidism, Familial Isolated

Genetic Tests for Hypoparathyroidism, Familial Isolated

Genetic tests related to Hypoparathyroidism, Familial Isolated:

# Genetic test Affiliating Genes
1 Hypoparathyroidism Familial Isolated 28 GCM2 PTH
2 Hypoparathyroidism, Autosomal Recessive 28

Anatomical Context for Hypoparathyroidism, Familial Isolated

MalaCards organs/tissues related to Hypoparathyroidism, Familial Isolated:

38
Thymus, Eye

Publications for Hypoparathyroidism, Familial Isolated

Articles related to Hypoparathyroidism, Familial Isolated:

(show all 30)
# Title Authors Year
1
The facial triad in the I+-ketoglutarate dependent oxygenase FIH: A role for sterics in linking substrate binding to O2 activation. ( 27815979 )
2017
2
Bone Status Among Patients With Nonsurgical Hypoparathyroidism, Autosomal Dominant Hypocalcaemia, and Pseudohypoparathyroidism: A Cohort Study. ( 29087612 )
2017
3
TCT-826 Prospective single center First In Human (FIH) clinical trial to evaluate the safety and effectiveness of a septal occluder with bioresorbable framework in patients with clinically significant atrial septum defect (ASD) or patent foramen ovale (PFO). ( 27970217 )
2016
4
FIH Regulates Cellular Metabolism through Hydroxylation of the Deubiquitinase OTUB1. ( 26752685 )
2016
5
Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways. ( 26972000 )
2016
6
Kinetic Investigations of the Role of Factor Inhibiting Hypoxia-inducible Factor (FIH) as an Oxygen Sensor. ( 26112411 )
2015
7
Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel. ( 25413349 )
2015
8
Expression and DNA methylation levels of prolyl hydroxylases PHD1, PHD2, PHD3 and asparaginyl hydroxylase FIH in colorectal cancer. ( 24195777 )
2013
9
Uncoupled O2-activation in the human HIF-asparaginyl hydroxylase, FIH, does not produce reactive oxygen species. ( 21443853 )
2011
10
Overexpression of the HIF hydroxylases PHD1, PHD2, PHD3 and FIH are individually and collectively unfavorable prognosticators for NSCLC survival. ( 21887331 )
2011
11
The chromatin remodeler ISWI regulates the cellular response to hypoxia: role of FIH. ( 21900490 )
2011
12
Factor-inhibiting hypoxia-inducible factor (FIH) catalyses the post- translational hydroxylation of histidinyl residues within ankyrin repeat domains. ( 21251231 )
2011
13
Consequences of IkappaB alpha hydroxylation by the factor inhibiting HIF (FIH). ( 21056038 )
2010
14
DNA methylation analysis of the HIF-1I+ prolyl hydroxylase domain genes PHD1, PHD2, PHD3 and the factor inhibiting HIF gene FIH in invasive breast carcinomas. ( 20727020 )
2010
15
miR-31 ablates expression of the HIF regulatory factor FIH to activate the HIF pathway in head and neck carcinoma. ( 20145132 )
2010
16
Expression of nuclear FIH independently predicts overall survival of clear cell renal cell carcinoma patients. ( 20709525 )
2010
17
Nutlin-3, an Hdm2 antagonist, inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated inactivation of HIF-1alpha. ( 19696166 )
2009
18
Proteomics-based identification of novel factor inhibiting hypoxia- inducible factor (FIH) substrates indicates widespread asparaginyl hydroxylation of ankyrin repeat domain-containing proteins. ( 18936059 )
2009
19
MYPT1, the targeting subunit of smooth-muscle myosin phosphatase, is a substrate for the asparaginyl hydroxylase factor inhibiting hypoxia- inducible factor (FIH). ( 19245366 )
2009
20
Abundance of aspargynyl-hydroxylase FIH is regulated by Siah-1 under normoxic conditions. ( 18280659 )
2008
21
Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1. ( 18174379 )
2008
22
A novel mode of action of YC-1 in HIF inhibition: stimulation of FIH-dependent p300 dissociation from HIF-1{alpha}. ( 19074848 )
2008
23
Evidence that two enzyme-derived histidine ligands are sufficient for iron binding and catalysis by factor inhibiting HIF (FIH). ( 18611856 )
2008
24
Overexpression of the oxygen sensors PHD-1, PHD-2, PHD-3, and FIH Is associated with tumor aggressiveness in pancreatic endocrine tumors. ( 18927305 )
2008
25
ASB4 is a hydroxylation substrate of FIH and promotes vascular differentiation via an oxygen-dependent mechanism. ( 17636018 )
2007
26
Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH). ( 17003112 )
2006
27
Use of novel monoclonal antibodies to determine the expression and distribution of the hypoxia regulatory factors PHD-1, PHD-2, PHD-3 and FIH in normal and neoplastic human tissues. ( 16324198 )
2005
28
Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4- hydroxylases. ( 14701857 )
2004
29
Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity. ( 15239670 )
2004
30
Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. ( 12042299 )
2002

Variations for Hypoparathyroidism, Familial Isolated

UniProtKB/Swiss-Prot genetic disease variations for Hypoparathyroidism, Familial Isolated:

71
# Symbol AA change Variation ID SNP ID
1 GCM2 p.Arg47Leu VAR_058044 rs104893959
2 GCM2 p.Gly63Ser VAR_058045 rs104893960
3 GCM2 p.Arg110Trp VAR_065495 rs780594439
4 GCM2 p.Asn502His VAR_065498 rs533942394
5 PTH p.Cys18Arg VAR_006047 rs104894271
6 PTH p.Ser23Pro VAR_018464 rs104894272

ClinVar genetic disease variations for Hypoparathyroidism, Familial Isolated:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PTH NM_000315.3(PTH): c.52T> C (p.Cys18Arg) single nucleotide variant Pathogenic rs104894271 GRCh37 Chromosome 11, 13514351: 13514351
2 PTH PTH, IVS2DS, G-C, +1, EX2DEL deletion Pathogenic
3 PTH NM_000315.3(PTH): c.67T> C (p.Ser23Pro) single nucleotide variant Pathogenic rs104894272 GRCh37 Chromosome 11, 13514336: 13514336
4 CASR NM_000388.3(CASR): c.1934C> A (p.Ala645Asp) single nucleotide variant Likely pathogenic rs193922430 GRCh37 Chromosome 3, 122002735: 122002735
5 GCM2 NM_004752.3(GCM2): c.893delT (p.Ile298Thrfs) deletion Pathogenic rs886037646 GRCh37 Chromosome 6, 10874856: 10874856
6 GCM2 GCM2, EX1-4DEL deletion Pathogenic
7 GCM2 NM_004752.3(GCM2): c.140G> T (p.Arg47Leu) single nucleotide variant Pathogenic rs104893959 GRCh37 Chromosome 6, 10877576: 10877576
8 GCM2 NM_004752.3(GCM2): c.187G> A (p.Gly63Ser) single nucleotide variant Pathogenic rs104893960 GRCh37 Chromosome 6, 10877529: 10877529
9 GCM2 NM_004752.3(GCM2): c.408C> A (p.Tyr136Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 6, 10876726: 10876726

Expression for Hypoparathyroidism, Familial Isolated

Search GEO for disease gene expression data for Hypoparathyroidism, Familial Isolated.

Pathways for Hypoparathyroidism, Familial Isolated

GO Terms for Hypoparathyroidism, Familial Isolated

Biological processes related to Hypoparathyroidism, Familial Isolated according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 9.13 AIRE GCM2 PTH
2 cellular calcium ion homeostasis GO:0006874 8.62 GCM2 PTH

Sources for Hypoparathyroidism, Familial Isolated

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