Case: IV-1

CasePresentingHPOsFreeText: Both affected subjects had symptoms of nonprogressive nyctalopia since childhood, while the proband also had photophobia. Both cases had a distance visual acuity of 20/50 or better in each eye, normal contrast sensitivity, and an incomplete type of Schubert-Bornschein ERGs. The proband also had high myopia, a mild red-green color deficit, hypopigmented fundus, and foveal hypoplasia with no evidence of chiasmal misrouting.

CasePreviousTesting:

CaseGenotypingMethod: Haplotype analysis was performed on all three members of the family using polymorphic microsatellite DNA markers flanking CACNA1F (DXS1003 and DXS7132. All exons and exon/intron boundaries of CACNA1F and nyctalopin (NYX) genes were sequenced in the proband (case IV 1)

Variant: c.1807G>C mutation (p.G603R)

ClinVarID: or CAID: CA412914688

gnomAD: not found in gnomAD v2.1.1

AddCaseInfo: The mutation is located on the S3 helical trans-membrane domain repeat II of the CACNA1F gene (CACNA1F encodes for the α1 subunit of a L-type Ca2+ channel that contains four repeat domains, each of which has six transmembrane domains (S1–S6); NP_005174.2). The p.G603R was predicted to be possibly damaging by Polyphen v. 2.09 with a PSIC score difference of 1.525. The mutation was predicted also to affect protein function by SIFT with a score of 0.00.

PreviouslyPublished:

Case: Patient 1

CasePresentingHPOsFreeText: A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a “square-wave” appearance in CSNB1 and a decreased b-wave in CSNB2. Patients with CSNB2 had rod- and cone-related problems. reduced visual acuity, nystagmus, symptoms of night blindness, or high refractive error at a young age.

CasePreviousTesting:

CaseGenotypingMethod: Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in CACNA1F and CABP4 in patients with CSNB2. The coding exons and flanking intron sequences of the different CSNB2 genes were amplified by standardized polymerase chain reaction.

Variant: c.1075G>A (p.Gly359Arg)

ClinVarID: or CAID: CA412919833

gnomAD: variant not present in gnomAD v2.1.1

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PreviouslyPublished:

VariantEvidence:

Case: Patient 5

CasePresentingHPOsFreeText: A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a “square-wave” appearance in CSNB1 and a decreased b-wave in CSNB2. Patients with CSNB2 had rod- and cone-related problems. reduced visual acuity, nystagmus, symptoms of night blindness, or high refractive error at a young age.

CasePreviousTesting:

CaseGenotypingMethod: Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in CACNA1F and CABP4 in patients with CSNB2. The coding exons and flanking intron sequences of the different CSNB2 genes were amplified by standardized polymerase chain reaction.

Variant: 1684+1G>A

ClinVarID: or CAID: CA412915988

gnomAD: variant not present in gnomAD v2.1.1

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PreviouslyPublished:

VariantEvidence:

Case: Patient 3

CasePresentingHPOsFreeText: A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a “square-wave” appearance in CSNB1 and a decreased b-wave in CSNB2. Patients with CSNB2 had rod- and cone-related problems. Patients with CSNB2 had rod- and cone-related problems. reduced visual acuity, nystagmus, symptoms of night blindness, or high refractive error at a young age.

CasePreviousTesting:

CaseGenotypingMethod: Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in CACNA1F and CABP4 in patients with CSNB2. The coding exons and flanking intron sequences of the different CSNB2 genes were amplified by standardized polymerase chain reaction.

Variant: c.208C>T (p.Arg70Trp)

ClinVarID: or CAID: CA412927449

gnomAD: not present in gnomAD v2.1.1

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PreviouslyPublished:

VariantEvidence:

Case: Patient 2

CasePresentingHPOsFreeText: A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a “square-wave” appearance in CSNB1 and a decreased b-wave in CSNB2. Patients with CSNB2 had rod- and cone-related problems. reduced visual acuity, nystagmus, symptoms of night blindness, or high refractive error at a young age.

CasePreviousTesting:

CaseGenotypingMethod: Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in CACNA1F and CABP4 in patients with CSNB2. The coding exons and flanking intron sequences of the different CSNB2 genes were amplified by standardized polymerase chain reaction.

Variant: c.952_954del (p.Phe318del)

ClinVarID: or CAID: CA645509415

gnomAD: variant not present in gnomAD v2.1.1

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PreviouslyPublished:

VariantEvidence:

Case: Patient 4

CasePresentingHPOsFreeText: A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a “square-wave” appearance in CSNB1 and a decreased b-wave in CSNB2. Patients with CSNB2 had rod- and cone-related problems. reduced visual acuity, nystagmus, symptoms of night blindness, or high refractive error at a young age.

CasePreviousTesting:

CaseGenotypingMethod: Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in CACNA1F and CABP4 in patients with CSNB2. The coding exons and flanking intron sequences of the different CSNB2 genes were amplified by standardized polymerase chain reaction.

Variant: c.1496+1G>A

ClinVarID: or CAID: CA412916990

gnomAD: variant not present in gnomAD v2.1.1

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PreviouslyPublished:

VariantEvidence:

Case: QT41

CasePresentingHPOsFreeText: nystagmus

CaseGenotypingMethod: WES

Variant: c.4347_4353del, p.Arg1449Serfs*36

ClinVarID: or CAID: CA2573332454

gnomAD: absent

AddCaseInfo: Male, onset=birth, severley reduced rod and cone ERG response