Amelogenesis imperfecta

Gene: STIM1

Green List (high evidence)

STIM1 (stromal interaction molecule 1)
EnsemblGeneIds (GRCh38): ENSG00000167323
EnsemblGeneIds (GRCh37): ENSG00000167323
OMIM: 605921, Gene2Phenotype
STIM1 is in 10 panels

3 reviews

Sarah Leigh (Genomics England Curator)

Comment when marking as ready: Associated with Immunodeficiency 10 phenotype in OMIM, not in G2P and included in the AI gene diagnostic panel. At least 6 variants reported.
4 Jan 2018, 1:08 p.m.
Comment on phenotypes: Immunodeficiency 10, 612783 (includes Hypomineralized amelogenesis imperfecta). Monoallelic variants associated with Myopathy, tubular aggregate, 1 OMIM 160565 and Stormorken syndrome OMIM 185070, to date these conditions do not include features of enamel defects
4 Jan 2018, 1:06 p.m.

Claire Smith (University of Leeds)

Green List (high evidence)

This gene is included in the AI gene diagnostic panel. This is available for NHS diagnostics from Yorkshire Regional Genetics.

Mutations in STIM1 and ORAI1 have been identified in patients with a variety of phenotypes including immunodeficiency, autoimmune disease, myopathy, anhydrosis / hypohydrosis and syndromic enamel defects (Feske et al. 2006, McCarl et al. 2009, Picard et al. 2009, Byun et al. 2010, Fuchs et al. 2012, Bohm et al. 2013, Hedberg et al. 2014, Nesin et al. 2014, Wang et al. 2014). Both dominant and recessive mutations in STIM1 and ORAI1 have been noted to cause pathology, however it is unclear whether the presence of enamel defects is always assessed or recorded since some patients die within the first year of life (McCarl et al. 2009). It is thought that dominant disease is a result of constitutive activation of STIM1 and ORAI1 leading to elevated intracellular calcium that does not appear to affect enamel maturation, but causes muscle and immunological phenotypes in isolation (Bohm et al. 2013, Nesin et al. 2014). In contrast, recessive disease appears to be the result of loss of function of STIM1 and ORAI1 that leads to depleted intracellular calcium and an enamel phenotype in addition to other pathology (Feske 2010, Wang et al. 2014).

Enamel defects have been reported for 4 families with biallelic STIM1 mutations (Picard et al. 2009, Fuchs et al. 2012, Wang et al. 2014, Parry et al. 2015).
17 Nov 2017, 12:57 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Amelogenesis imperfecta; Immunodeficiency 10 OMIM 612783; Myopathy, tubular aggregate, 1 OMIM 160565 (monoallelic); Stormorken syndrome (monoallelic) OMIM 185070

Publications

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Red to Green: On 'prior genetic testing' inclusion list. Sufficient (>3) cases of STIM1 variants causing 'Immunodeficiency 10, 612783' which can present with AI. PMID:24621671 provides a case where AI is a prominent feature of a proband. Mouse model with enamel defects presented in PMID:28732182 (2017), plus functional studies show a role for STIM1 in enamel maturation.
23 Oct 2017, 10:50 a.m.
PMID:24621671 (2014) report a 6 year old female proband with syndromic hypomaturation enamel defects caused by a homozygous C to T transition (g.232598C>T c.1276C>T p.Arg426Cys) in STIM1.
23 Oct 2017, 10:48 a.m.
Immunodeficiency 10 (MIM:612783) is characterised by recurrent childhood infections. Affected individuals
may also have dental enamel hypoplasia consistent with amelogenesis imperfecta.
23 Oct 2017, 7:59 a.m.
Comment on mode of inheritance: Biallelic MOI supported by OMIM.
23 Oct 2017, 7:54 a.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Immunodeficiency 10, 612783
OMIM
605921
Clinvar variants
Variants in STIM1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

2 Feb 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

This panel has been promoted after review by Claire Smith (Leeds) and further personal consultation with Dr Smith

4 Jan 2018, Gel status: 3

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

4 Jan 2018, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for STIM1 were set to Immunodeficiency 10, 612783

4 Jan 2018, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for STIM1 were set to 28732182; 24621671; 26560041; 19420366; 22190180

5 Dec 2017, Gel status: 3

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

23 Oct 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for STIM1 were set to 28732182; 24621671

23 Oct 2017, Gel status: 4

Set publications

Rebecca Foulger (Genomics England curator)

Publications for STIM1 were set to 28732182

23 Oct 2017, Gel status: 4

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Green List (High Evidence).

23 Oct 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for STIM1 was changed to BIALLELIC, autosomal or pseudoautosomal

23 Oct 2017, Gel status: 1

Set Mode of Inheritance

Rebecca Foulger (Genomics England curator)

Mode of inheritance for STIM1 was changed to BIALLELIC, autosomal or pseudoautosomal

23 Oct 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for STIM1 were set to Immunodeficiency 10, 612783 (includes Hypomineralized amelogenesis imperfecta)

8 Jun 2017, Gel status: 1

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

STIM1 was added to Amelogenesis Imperfectapanel. Source: UKGTN Model of inheritance for gene STIM1 was set to BIALLELIC, autosomal or pseudoautosomal

8 Jun 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

STIM1 was created by rfoulger

8 Jun 2017, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

STIM1 was added to Amelogenesis Imperfectapanel. Sources: Eligibility statement prior genetic testing