Case#: T.II.1, subject 48. Male. Age of Onset: 1.5 y.o. Age of evaluation: 21 y.o. Origin in UK, Caucasian.

*DiseaseAssertion: Cytopenia, Evans syndrome

*FamilyInfo: Father had died post autologous HSCT for non-Hodgkin lymphoma. See "supplement 1".

CasePresentingHPOs: ORPHA:1959

CaseHPOFreeText: Severe Psoriatic Arthritis (only patient noted to have it within the study), received a Hematopoietic stem cell transplantation and was one of nine affected mutation carriers still alive and one of three who was more than five years post-HSCT and currently well off all medication at the time of publication.

*CaseNotHPOs: large phenotype table with unreported symptoms in table S1

*CaseNotHPOFreeText: Patient was checked for a number of additional phenotypes but none were identified. Please see Supplementary table S1 for details.

CasePreviousTesting: Genome-wide methods were not used (sequencing of CTLA4 was performed, but no reference made to other genes tested). Some families received whole-exome sequencing but we are unsure if this patient was included.

GenotypingMethod: The authors imply that they sequenced the four exons of CTLA4.

PreviouslyPublished: Yes, Slatter, et al. PMID: 27102614

Variant: c.518G>A, p.G173E

ClinVarID: N/A

CAID: CA350138990

gnomAD: Not Found

SupplementalData: extensive data in S1

Note: Not functionally tested using transendocytosis

Case#: AAA.II.1, subject 130. Male. Age of Onset: 23y.o. Age of evaluation: 46 y.o. Origin in Switzerland, Caucasian.

DiseaseAssertion: Gastrointestinal involvement

FamilyInfo: None found

CasePresentingHPOs: HP:0008207 (Addison's disease), HP:0004313 (Hypogammaglobulinemia), HP:0002720 (Low IgA), HP:0002014 (Diarrhea), HP:0002242 (Enteropathy), HP:0012410 (PRCA/Pure red cell aplasia)

CaseHPOFreeText: Lymphoproliferation, Cytopenia, Autoimmune cytopenia, Endocrinological involvement, Kidney involvement

Lymphocytic or granulomatous organ infiltration of the gut

Thirty-five percent of affected mutation carriers (27/78) were under antibiotic prophylaxis. In one affected mutation carrier (the patient) treatment with vedolizumab (blocking α4β7 integrin) improved colitis, and in the same individual PRCA responded well to cyclosporine A.

IgG levels: no values were available before IVIG or Rituximab

CaseNotHPOs: large phenotype table with unreported symptoms in table S1

CaseNotHPOFreeText: Patient was checked for a number of additional phenotypes but none were identified. Please see Supplementary table S1 for details.

CasePreviousTesting: Genome-wide methods were not used (sequencing of CTLA4 was performed, but no reference made to other genes tested). Some families received whole-exome sequencing but we are unsure if this patient was included.

GenotypingMethod: The authors imply that they sequenced the four exons of CTLA4.

PreviouslyPublished: Yes, Navarini et al. PMID: 27908448

Variant: NM_005214.5:c.257C>T

ClinVarID: 661941

CAID: CA2067080

gnomAD: 2:204735456 C / T

SupplementalData: extensive data in S1

Note: Functionally tested using transendocytosis

Performed a meta-analysis of all data published on the rs2710102 CNTNAP2 variant up to 2015, and included Anney et al, 2012 (PMID: 20663923), Toma et al., 2013 (PMID: 23277129), Sampath et al, 2013 (PMID: 24147096), Poot et al., 2014 (PMID: 25337070 ), plus there current cohort.

No significant increase in cases vs controls for CNTNAP2 rs2710102

While this data does help support Contradictory evidence for CNTNAP2 involvement in autism, the lack of reporting of the total number of controls, as well as the number of cases and controls with the SNP prevents me from curating this information within the ClinGen gene curation interface.

Performed a meta-analysis of all data published on the rs7794745 CNTNAP2 variant up to 2015, and included Arking et al., 2008 (PMID:18179894), Li et al 2010 (PMID: 20414140), Anney et al, 2012 (PMID: 20663923), Toma et al., 2013 (PMID: 23277129), Sampath et al, 2013 (PMID: 24147096), plus there current cohort.

No significant increase in cases vs controls for CNTNAP2 rs7794745

Annotating here since the full text is a PDF.

Case#: Family AR321 proband, US, 6yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: proband and two other siblings are affected

CasePresentingHPOs: The essential and defining features of STGD were (1) pedigrees with at least one living affected individual compatible with autosomal recessive inheritance; (2) an ophthalmoscopically characteristic retinal disorder in families with both parents living; (3) bilateral central visual loss with both “beaten metal” elliptical foveal dystrophy and temporal pallor of the optic discs, documented by retinal color photography, with or without yellow-pigment epithelial flecks in the macular and/or retinal “near periphery”; and (4) the characteristic fluorescein angiographic feature of a dark choroid (Blacharski 1988).

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: (1) evidence of autosomal dominant inheritance; (2) any history of night blindness, loss of peripheral vision, or "retinitis pigmentosa"; (3) cataracta complicata or cells in the vitreous; (4) substantially abnormal electroretinographic or electrooculographic responses; (5) no fluorescein angiography performed or no dark choroid documented; (6) neurological disease (including loss of cognition or seizures); 7) drug exposures (especially to antimalarial and agents known to cause crystalline retinopathies); or (8) any "atypical" maculopathies in which a unique diagnosis of STGD could not be established.

PreviouslyPublished: PMID: 8533764

Variant: c.3113C>T p.A1038V; c.1715G>C p.R572P . Heteroduplex and SSCP analyses were used to screen the 50 exons of ABCA4. Linkage analysis and haplotype analysis were previously performed

ClinVar: 99073

CAID: CA226919

SupplementalData: n/a

Didn't segregate with disease, an affected family member lacks ABCA4 variant.