Intracerebral calcification disorders

Gene: AP1S2

Green List (high evidence)

AP1S2 (adaptor related protein complex 1 sigma 2 subunit)
EnsemblGeneIds (GRCh38): ENSG00000182287
EnsemblGeneIds (GRCh37): ENSG00000182287
OMIM: 300629, Gene2Phenotype
AP1S2 is in 15 panels

2 reviews

Ellen Thomas (Genomics England Curator)

Comment on list classification: Calcifications may be present in this condition.
Created: 19 Dec 2016, 4:48 p.m.

Ellen McDonagh (Genomics England Curator)

Comment on list classification: No expert review at this time - It is a green gene on the Intellectual disability gene panel (version 1.14) and Hereditary ataxia gene panel (version 1.34), with 4 family reports with evidence of calcification.
Created: 29 Nov 2016, 12:28 p.m.

Details

Mode of Inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Emory Genetics Laboratory
Phenotypes
  • Calcifications in basal ganglia
OMIM
300629
Clinvar variants
Variants in AP1S2
Penetrance
Complete
Publications
  • 17617514 - identification of AP1S2 variants in a large 4-generation French family, and a Scottish family, marked calcifications of the basal ganglia were reported in affected individuals in both families
  • 18428203 - an additional two families reported "Studying four patients in two unrelated families in which AP1S2 nonsense and splicesite mutations segregated, we found that affected individuals presented, in addition to previously described features, with elevated protein levels in cerebrospinal fluid (CSF). Moreover, computed tomography scans demonstrated that the basal ganglia calcifications associated with AP1S2 mutations appeared during childhood and might be progressive. Based on these observations, we propose that AP1S2 mutations are responsible for a clinically recognizable XLMR and autism syndrome associating hypotonia, delayed walking, speech delay, aggressive behavior, brain calcifications, and elevated CSF protein levels."
Panels with this gene

History Filter Activity

19 Dec 2016, Gel status: 4

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

19th Dec 2016: panel revised according to expert review and internal curation review.

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

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

19 Dec 2016, Gel status: 4

Set Mode of Inheritance

Ellen Thomas (Genomics England Curator)

Mode of inheritance for AP1S2 was changed to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

19 Dec 2016, Gel status: 4

Gene classified by Genomics England curator

Ellen Thomas (Genomics England Curator)

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

29 Nov 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for AP1S2 were set to 17617514 - identification of AP1S2 variants in a large 4-generation French family, and a Scottish family, marked calcifications of the basal ganglia were reported in affected individuals in both families; 18428203 - an additional two families reported "Studying four patients in two unrelated families in which AP1S2 nonsense and splicesite mutations segregated, we found that affected individuals presented, in addition to previously described features, with elevated protein levels in cerebrospinal fluid (CSF). Moreover, computed tomography scans demonstrated that the basal ganglia calcifications associated with AP1S2 mutations appeared during childhood and might be progressive. Based on these observations, we propose that AP1S2 mutations are responsible for a clinically recognizable XLMR and autism syndrome associating hypotonia, delayed walking, speech delay, aggressive behavior, brain calcifications, and elevated CSF protein levels."

29 Nov 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for AP1S2 were set to 17617514 - identification of AP1S2 variants in a large 4-generation French family, and a Scottish family, marked calcifications of the basal ganglia were reported in affected individuals in both families; 18428203 - an additional two families reported.

29 Nov 2016, Gel status: 2

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for AP1S2 were set to 17617514 -;18428203

29 Nov 2016, Gel status: 2

Gene classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

29 Nov 2016, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for AP1S2 were set to 17617514; 18428203 - "computed tomography scans demonstrated that the basal ganglia calcifications associated with AP1S2 mutations appeared during childhood and might be progressive. Based on these observations, we propose that AP1S2 mutations are responsible for a clinically recognizable XLMR and autism syndrome associating hypotonia, delayed walking, speech delay, aggressive behavior, brain calcifications, and elevated CSF protein levels."

29 Nov 2016, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for AP1S2 were set to 17617514; 18428203 - "omputed tomography scans demonstrated that the basal ganglia calcifications associated with AP1S2 mutations appeared during childhood and might be progressive. Based on these observations, we propose that AP1S2 mutations are responsible for a clinically recognizable XLMR and autism syndrome associating hypotonia, delayed walking, speech delay, aggressive behavior, brain calcifications, and elevated CSF protein levels."

29 Nov 2016, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for AP1S2 were set to 17617514; 18428203

25 Aug 2016, Gel status: 1

Added New Source

Olivia Niblock (Genomics England Curator)

AP1S2 was added to Intracerebral calcification disorderspanel. Sources: Emory Genetics Laboratory

25 Aug 2016, Gel status: 0

Created

Olivia Niblock (Genomics England Curator)

AP1S2 was created by oniblock