Intracerebral calcification disorders (Version 1.35)

Description

Intracerebral calcification disorders inclusion criteria (36622)
•	Intracerebral calcification identified on brain imaging in the absence of a known genetic cause.

Intracerebral calcification disorders exclusion criteria (36622)
•	Known genetic diagnosis.
•	Evidence of causative environmental cause, for example infection
•	Phenotype indicative of other recruitable rare disorder, for example Cockayne syndrome

Prior genetic testing guidance (36622)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Intracerebral calcification disorders prior genetic testing genes (36622)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
 -	Guided by phenotype, for example UKGTN Aidcardi-Goutieres syndrome gene panel testing

Closing statement (36622)
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

12 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Richard Scott (Genomics England Curator)

Group: Other
Workplace: Other
Ellen Thomas (Genomics England Curator)

Group: Other
Workplace: Other
Yanick Crow (University of Manchester)

Group: GeCIP domain
Workplace: Other clinical service
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Cristina Dias (The Francis Crick Institute)

Group: NHS Genomic Medicine Centre
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Zornitza Stark (Australian Genomics)

Group: Other
Workplace: Other clinical service
Anna de Burca (Genomics England Curator)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Raquel Real (UCL Queen Square Institute of Neurology)

Group: GeCIP domain
Workplace: Research lab
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other

33 Entities

33 reviewed, 25 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 33 Entitiess
Green Green List (high evidence)	ACP5	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spondyloenchondrodysplasia with immune dysregulation Spondyloenchondrodysplasia, short stature, SLE, intracranial calcification, spasticity, chilblains, autoimmune haemolytic anaemia Tags
Green Green List (high evidence)	ADAR	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Expert list Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Aicardi-Goutieres syndrome 6, OMIM:615010 Dyschromatosis symmetrica hereditaria, OMIM:127400 Tags
Green Green List (high evidence)	AP1S2	2 reviews	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Pettigrew syndrome, OMIM:304340 Calcifications in basal ganglia Tags
Green Green List (high evidence)	COL4A1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes Porencephaly 1 Variable phenotype - porencephaly, destructive cerebral lesions, eye anomalies, intracerebral calcification Tags
Green Green List (high evidence)	CTC1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Cerebroretinal microangiopathy with calcifications and cysts, 612199 Coats Plus syndrome Tags
Green Green List (high evidence)	CYP2U1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Spastic paraplegia 56, autosomal recessive Tags
Green Green List (high evidence)	FARSA	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes ?Rajab interstitial lung disease with brain calcifications 2, OMIM:619013 Tags
Green Green List (high evidence)	FARSB	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Rajab syndrome, MIM#613658 interstitial lung disease brain calcifications microcephaly intellectual disability Tags
Green Green List (high evidence)	IFIH1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Eligibility statement prior genetic testing Expert list Expert Review Green UKGTN Phenotypes Aicardi-Goutieres syndrome 7, OMIM:615846 Tags
Green Green List (high evidence)	JAM3	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Hemorrhagic destruction of the brain, subependymal calcification, and cataracts, 613730 Tags
Green Green List (high evidence)	KIAA1161	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Primary Familial Brain Calcification Basal ganglia calcification, idiopathic, 7, autosomal recessive, 618317 Tags gene-checked new-gene-name
Green Green List (high evidence)	NRROS	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Seizures, early-onset, with neurodegeneration and brain calcification 618875 Tags
Green Green List (high evidence)	OCLN	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Band-like calcification with simplified gyration and polymicrogyria Band-like calcification with simplified gyration and polymicrogyria, 251290 Severe developmental delay with microcephaly Tags structural-variant
Green Green List (high evidence)	PDGFB	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Basal ganglia calcification, idiopathic, 5, 615483 Fahr syndrome Tags
Green Green List (high evidence)	PDGFRB	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Emory Genetics Laboratory Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Basal ganglia calcification idiopathic 4, 615007 Calcifications in basal ganglia Fahr syndrome Tags
Green Green List (high evidence)	RNASEH2A	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Other UKGTN Phenotypes Aicardi-Goutieres syndrome 4 Aicardi-Goutieres Syndrome Tags
Green Green List (high evidence)	RNASEH2B	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Other UKGTN Phenotypes Aicardi-Goutieres syndrome 2, OMIM:610181 Tags
Green Green List (high evidence)	RNASEH2C	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Other UKGTN Phenotypes Aicardi-Goutieres syndrome 3 Aicardi-Goutieres Syndrome Tags
Green Green List (high evidence)	SAMHD1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Emory Genetics Laboratory Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Aicardi-Goutieres syndrome Aicardi-Goutieres Syndrome Tags
Green Green List (high evidence)	SLC20A2	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Basal ganglia calcification, idiopathic, 1, 213600 Familial Idiopathic Basal Ganglia Calcification Fahr syndrome Tags deletions
Green Green List (high evidence)	TINF2	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes Revesz syndrome, 268130 Tags
Green Green List (high evidence)	TREM2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Green Phenotypes Calcifications in basal ganglia Nasu-Hakola disease Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) Tags
Green Green List (high evidence)	TREX1	2 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Other UKGTN Phenotypes Aicardi-Goutieres syndrome 1, dominant and recessive Aicardi-Goutières syndrome, isolated chilblains, lupus-like disease, retinal vasculopathy with cerebral leukodystrophy Tags
Green Green List (high evidence)	USP18	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes pseudo-TORCH syndrome Tags
Green Green List (high evidence)	XPR1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green Literature Radboud University Medical Center, Nijmegen Phenotypes Basal ganglia calcification (Fahr syndrome) Basal ganglia calcification, idiopathic, 6, 616413 Tags
Red Red List (low evidence)	ERCC6	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Intercranial Calcifications Tags
Red Red List (low evidence)	MAT1A	1 review	Not set	Sources Emory Genetics Laboratory Expert Review Red Phenotypes Calcifications in basal ganglia Methionine adenosyltransferase deficiency, autosomal recessive Tags
Red Red List (low evidence)	PCDH12	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Phenotypes intellectual disability microcephaly epilepsy perithalamic hyperechogenicity periventricular hyperechogenicity midbrain abnormalities hypothalamic abnormalities Tags founder-effect
Red Red List (low evidence)	SCN2A	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Literature Phenotypes Epileptic encephalopathy, early infantile, 11 Seizures, benign familial infantile, 3 Tags
Red Red List (low evidence)	SNORD118	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Phenotypes 614561 Tags locus-type-small-nucleolar
No list No list	JAM2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Literature Phenotypes Primary brain calcification Tags
No list No list	RNASET2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Phenotypes Leukoencephalopathy, cystic, without megalencephaly, MIM# 612951 Tags
No list No list	TYROBP	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Phenotypes Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, MIM# 221770 Tags

Major version comments

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

Intracerebral calcification disorders (Version 1.35)

12 reviewers

33 Entities

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