PMID: 14609846

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

Case#: Allen_2003_Familly_X08_Proband, male, age not mentioned, British national origin

CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

CaseHPOFreeText: ERG with absent scotopic oscillatory potential, subnormal ON response

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal OFF response

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing of PCR-amplified exons from NYX and CACNA1F

CaseMethod2: Haplotype analysis using microsatellite markers surrounding the NYX locus

CaseGenotypingMethod: The proband and family members were subjected to Sanger sequencing of NYX to identify the variant, followed by microsatellite-based haplotype analysis of families sharing the same variant.

Variant: The proband harbors the NM_022567.2(NYX):c.895C>T (p.Gln299Ter) variant on the X chromosome.

CAID: CA412991558

gnomAD: NM_022567.2(NYX):c.895C>T (p.Gln299Ter) was not found in gnomAD.

VariantEvidence: NM_022567.2(NYX):c.895C>T (p.Gln299Ter) is a nonsense variant in exon 3/3 that is not predicted to trigger NMD but truncates the C-terminal 38% of the protein product. A separate publication (PMID: 14507859) indicates that variants (such as this one) that remove the C-terminal GPI anchor disrupt NYX function by triggering its mislocalization to and accumulation in the ER and Golgi and its absence from its normal destination at the cell surface.

CaseAddInfo: N/A

CasePMIDs: N/A

Case#: Allen_2003_Familly_X05_Proband, male, age not mentioned, British national origin

CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

CaseHPOFreeText: ERG with absent scotopic oscillatory potential, subnormal ON response

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal OFF response

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing of PCR-amplified exons from NYX and CACNA1F

CaseMethod2: Haplotype analysis using microsatellite markers surrounding the NYX locus

CaseGenotypingMethod: The proband and family members were subjected to Sanger sequencing of NYX to identify the variant, followed by microsatellite-based haplotype analysis of families sharing the same variant.

Variant: The proband harbors the NM_022567.2(NYX):c.1122_*11del (p.Ser374ArgfsTer10) variant on the X chromosome.

CAID: CA2573050969

gnomAD: NM_022567.2(NYX):c.1122_*11del (p.Ser374ArgfsTer10) was not found in gnomAD.

VariantEvidence: NM_022567.2(NYX):c.1122_*11del (p.Ser374ArgfsTer10) is a frameshift variant in exon 3/3 that is not predicted to trigger NMD but disrupts the C-terminal 22% of the protein product. A separate publication (PMID: 14507859) indicates that variants (such as this one) that remove the C-terminal GPI anchor disrupt NYX function by triggering its mislocalization to and accumulation in the ER and Golgi and its absence from its normal destination at the cell surface. This is a recurrent variant reported here in multiple apparently unrelated British families (X05 and X09).

CaseAddInfo: N/A

CasePMIDs: N/A

Case#: Allen_2003_Familly_X03_Proband, male, age not mentioned, British national origin

CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

CaseHPOFreeText: ERG with absent scotopic oscillatory potential, subnormal ON response

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal OFF response

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing of PCR-amplified exons from NYX and CACNA1F

CaseMethod2: Haplotype analysis using microsatellite markers surrounding the NYX locus

CaseGenotypingMethod: The proband and family members were subjected to Sanger sequencing of NYX to identify the variant, followed by microsatellite-based haplotype analysis of families sharing the same variant.

Variant: The proband harbors the NM_022567.2(NYX):c.37+1G>C (p.=) variant on the X chromosome.

CAID: CA412988630

gnomAD: NM_022567.2(NYX):c.37+1G>C (p.=) was not found in gnomAD.

VariantEvidence: This splice site variant disrupts a canonical splice site between the two coding exons (exon 2 and exon 3), and is therefore predicted to disrupt the protein product.

CaseAddInfo: N/A

CasePMIDs: N/A

Case#: Allen_2003_Familly_X04_Proband, male, age not mentioned, British national origin

CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

CaseHPOFreeText: ERG with absent scotopic oscillatory potential, subnormal ON response

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal OFF response

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing of PCR-amplified exons from NYX and CACNA1F

CaseMethod2: Haplotype analysis using microsatellite markers surrounding the NYX locus

CaseGenotypingMethod: The proband and family members were subjected to Sanger sequencing of NYX to identify the variant, followed by microsatellite-based haplotype analysis of families sharing the same variant.

Variant: The proband harbors the NM_022567.2 (NYX):c.339_353del (p.Glu114_Ala118del) variant on the X chromosome.

CAID: CA2573050968

gnomAD: NM_022567.2 (NYX):c.339_353del (p.Glu114_Ala118del) was not found in gnomAD.

VariantEvidence: NM_022567.2:c.339_353del is an in-frame deletion variant that removes 5 amino acids from the center of the polypeptide sequence. It is a recurrent variant reported here in multiple apparently unrelated British families (X04 and X06).

CaseAddInfo: N/A

CasePMIDs: N/A

Case#: Pusch_2000_Family_9069_proband, male, 18 years of age, Swedish family origin

CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

CaseHPOFreeText: ERG with absent oscillatory-potential wavelets

CaseNotHPOs: HP:0001098 (Abnormal fundus morphology), HP:0030473 (Abnormal light-adapted flicker electroretinogram)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Linkage analysis and haplotype analysis were performed using RFLP X-chromosomal markers and SSCP.

CaseMethod1: Sanger sequencing of PCR amplified exons from NYX

CaseMethod2: N/A

CaseGenotypingMethod: Linkage analysis and haplotype analysis were performed using RFLP X-chromosomal markers and SSCP. This was followed by Sanger sequencing of PCR products to identify the variant.

Variant: The proband harbors the NM_022567.2(NYX):c.559_560delinsAA (p.Ala187Lys) variant in his X-chromosome.

ClinVar: 11423

gnomAD: NM_022567.2(NYX):c.559_560delinsAA (p.Ala187Lys) was not found in gnomAD.

VariantEvidence: This is missense variant does not have experimental evidence of impact on the protein product, but is a recurrent variant observed in this paper in multiple Swedish families (2996, 9069, and 2999) with a shared haplotype.

CaseAddInfo: Phenotype information is found in PMID: 12397430.

CasePMIDs: 12397430

Case#: Pusch_2000_Family_2438B_proband, male, 36 years of age, origin not mentioned (PMID: 12397430)

CasePresentingHPOs: HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

CaseHPOFreeText: ERG with absent oscillatory-potential wavelets

CaseNotHPOs: HP:0001098 (Abnormal fundus morphology), HP:0030473 (Abnormal light-adapted flicker electroretinogram)

CaseNotHPOFreeText: N/A

CasePreviousTesting: Linkage analysis and haplotype analysis were performed using RFLP X-chromosomal markers and SSCP.

CaseMethod1: Sanger sequencing of PCR amplified exons from NYX

CaseMethod2: N/A

CaseGenotypingMethod: Linkage analysis and haplotype analysis were performed using RFLP X-chromosomal markers and SSCP. This was followed by Sanger sequencing of PCR products to identify the variant.

Variant: The proband harbors the NM_001378477.3(NYX):c.77G>C (p.Cys26Ser) variant in his X-chromosome.

ClinVar: 99843

gnomAD: NM_001378477.3(NYX):c.77G>C (p.Cys26Ser) was not found in gnomAD.

VariantEvidence: This is missense variant does not have experimental evidence of impact on the protein product, but is a recurrent variant observed in multiple apparently unrelated families (2438B, 5886, and 5884) from this paper.

CaseAddInfo: Phenotype information is found in PMID: 12397430.

CasePMIDs: 12397430

Case#: Pusch_2000_Familly_9606_Proband, male, age and race not mentioned

CasePresentingHPOs: HP:0030640 (Complete congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

CaseHPOFreeText: ERG with absent oscillatory-potential wavelets

CaseNotHPOs: HP:0001098 (Abnormal fundus morphology), HP:0030473 (Abnormal light-adapted flicker electroretinogram)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing of PCR amplified exons from NYX

CaseMethod2: N/A

CaseGenotypingMethod: The proband and family members were subjected to Sanger sequencing of NYX to identify the variant.

Variant: The proband harbors the NM_001378477.3(NYX):c.90C>A (p.Cys30Ter) variant on the X chromosome.

ClinVar: 11422

gnomAD: NM_001378477.3(NYX):c.90C>A (p.Cys30Ter) was not found in gnomAD.

VariantEvidence: This nonsense variant is located in exon 2/3 and is predicted to trigger NMD. It introduces a premature stop codon that would truncate 93% of the protein product.

CaseAddInfo: This variant appears not only in Family 9606, but also in Family 2438T, yet is not suspected to be a founder alelle.

CasePMIDs: N/A

PMID: 11062472

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

PMID: 17881478

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

ExperimentName: Rescue of Nyx loss-of-function mouse by transgene expression in depolarizing bipolar cells of the retina

RescueModel: Mus musculus

GeneAlteration: This naturally occurring model, previously known to exhibit the absence of b-wave in ERG recordings, harbors an 85-bp deletion in the final exon of the Nyx gene that shifts the frame and replaces the C-terminal 61% of the protein product with 170 novel amino acids. The predicted effect is loss-of-function.

RescueVariant: Rescue was performed with a wild-type Nyx transgene, rather than a variant.

RescuePhenotype: HP:0007984 (Electronegative electroretinogram), HP:0000649 (Abnormality of visual evoked potentials), HP:0007663 (Reduced visual acuity)

RescueMethod: An EYFP-tagged mouse Nyx gene was placed under the control of the mouse GABAcp1 promoter for tissue-specific expression in bipolar cells of the retina, including rod and cone depolarizing and hyperpolarizing bipolar cells. The transgene was introduced by pronuclear injection to generate transgenic lines, then crossed to homozygous Nyx mice to yield transgenic male offspring with Nyx disruption.

RescueEvidence: The EYFP-Nyx transgene restores both the ERG b-wave (Figure 5B) and the spontaneous and light-evoked responses of retinal ganglion cells (Figure 6) in Nyx-deficient mice.

ModelVariant: The model is naturally occurring, and so the affected animals harbor a variant that does not have an exact human patient equivalent.

PMID: 15331616

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

PMID: 12506099

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

ExperimentName: Naturally occurring mouse model of Nyx loss-of-function

NonHumanModel: Mus musculus

GeneAlteration: This naturally occurring model, previously known to exhibit the absence of b-wave in ERG recordings, harbors an 85-bp deletion in the final exon of the Nyx gene that shifts the frame and replaces the C-terminal 61% of the protein product with 170 novel amino acids. The predicted effect is loss-of-function.

ModelPhenotype: HP:0007984 (Electronegative electroretinogram), HP:0000649 (Abnormality of visual evoked potentials), HP:0007663 (Reduced visual acuity), HP:0001419 (X-linked recessive inheritance)

HumanPhenotype: HP:0030640 (Complete congenital stationary night blindness), HP:0030469 (Abnormal dark-adapted electroretinogram), HP:0007642 (Congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0031624 (Moderate myopia), HP:0007984 (Electronegative electroretinogram)

ModelEvidence: The model exhibited reduced amplitude of dark-adapted bright flash electroretinogram b-wave (electronegative ERG) but normal amplitude of the a-wave (PMID: 9804152). Visually-driven cortical activity was also abnormal (9804152). Visual acuity was also reduced (Figure 4). Inheritance was X-linked recessive (Figure 3), which also matches the human families.

ModelVariant: The model is naturally occurring, and so the affected animals harbor a variant that does not have an exact human patient equivalent.

Case#: Bech-Hansen_2000_Patient_610-1, male, age and race not mentioned, national origin in Costa Rica

CasePresentingHPOs: HP:0030640 (Complete congenital stationary night blindness)

CaseHPOFreeText: Patients in this study have a diagnosis of complete congenital stationary night blindness. Although this implies nyctalopia and photopic vision loss, specific phenotypic details are absent.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Linkage analysis was performed using 17 X-chromosomal restriction fragment length polymorphism markers.

CaseMethod1: FokI restriction enzyme digestion of the relevant PCR product to monitor segregation in the proband and family members

CaseMethod2: Sanger sequencing of PCR amplified exons from NYX

CaseGenotypingMethod: Linkage analysis was initially performed using 17 X-chromosomal restriction endonuclease-based markers. The proband and family members were then subjected to restriction enzyme analysis of PCR products and Sanger sequencing to identify the variant.

Variant: The proband harbors the NM_001378477.3(NYX):c.1034G>A (p.Trp345Ter) variant on the X chromosome.

ClinVar: 11421

gnomAD: NM_001378477.3(NYX):c.1034G>A (p.Trp345Ter) has a maximum allele frequency of 0.00007388 (2/27070, with no males or homozygous females) in the Latino / Admixed American population. https://gnomad.broadinstitute.org/variant/X-41333755-G-A

VariantEvidence: This nonsense variant is located in the final exon and is not predicted to trigger NMD, but introduces a premature stop codon that truncates 28% of the protein product. The disrupted region is part of the predicted GPI anchor responsible for tethering the protein to the membrane.

CaseAddInfo: N/A

CasePMIDs: N/A

Case#: Bech-Hansen_2000_Family_R5_proband, male, age and race not mentioned, national origin in the United States

CasePresentingHPOs: HP:0030640 (Complete congenital stationary night blindness), HP:0030469 (Abnormal dark-adapted electroretinogram)

CaseHPOFreeText: At least one of two ERG abnormalities were observed in each affected family member; absence of rod psychophysical dark adaptation and/or absence of rod ERG with low-intensity blue flash.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Linkage analysis was originally performed in PMID: 2574143 using 17 X-chromosomal restriction fragment length polymorphism markers.

CaseMethod1: Agarose gel electrophoresis of the relevant PCR product to monitor segregation in the proband and family members

CaseMethod2: Sanger sequencing of PCR amplified exons from NYX

CaseGenotypingMethod: Linkage analysis was initially performed in PMID: 2574143 using 17 X-chromosomal restriction endonuclease-based markers. The proband and family members were then subjected to gel electrophoresis analysis of PCR products and Sanger sequencing to identify the variant.

Variant: The proband harbors the NM_001378477.3(NYX):c.70_93del (p.Arg24_Ala31del) variant on the X chromosome.

ClinVar: 99841

gnomAD: NM_001378477.3(NYX):c.70_93del (p.Arg24_Ala31del) has a maximum allele frequency of 0.0001018 (1/9823, with no males or homozygous females) in the European non-Finnish population https://gnomad.broadinstitute.org/variant/X-41332781-GGCCTGCGCCCGCGCTTGTCCCGCC-G

VariantEvidence: This in-frame deletion variant does not have experimental evidence of impact on the protein product, but is a recurrent variant observed in multiple apparently unrelated families (PMID: 2574143 and Figure 5 from this paper).

CaseAddInfo: Family phenotypes were described in PMID: 2574143.

CasePMIDs: PMID: 2574143

FamilyLabel: Bech-Hansen_2000_Family_R5

Family#PresentingHPOs: HP:0030640 (Complete congenital stationary night blindness), HP:0030469 (Abnormal dark-adapted electroretinogram)

Family#PresentingHPOFreeText: At least one of two ERG abnormalities were observed in each affected family member; absence of rod psychophysical dark adaptation and/or absence of rod ERG with low-intensity blue flash

FamilyNotHPOs: N/A

CountryOrigin: The United States

Ethnicity: Not mentioned

Race: Not mentioned

Family#PreviousTesting: Linkage analysis was originally performed in PMID: 2574143 using 17 X-chromosomal restriction fragment length polymorphism markers.

Family#Method1: Agarose gel electrophoresis of the relevant PCR product to monitor segregation in family members

Family#Method2: Sanger sequencing of PCR amplified exons from NYX

Family#GenotypingMethod: Linkage analysis was initially performed in PMID: 2574143 using 17 X-chromosomal restriction endonuclease-based markers. Family members were then subjected to gel electrophoresis analysis of PCR products and Sanger sequencing to identify the variant.

Affected: 4

Unaffected: 5

Segregations: 6 segregations (all consistent) among genotyped individuals are shown in this paper (pedigree in Fig. 3).

PublishedLOD: 7.35 (in PMID: 2574143, combined from 7 families)

eLOD: 1.8

AddSegregationInfo: N/A

ProbandLabel: Bech-Hansen_2000_Family_R5_proband

Variant: Affected male family members harbor the NM_001378477.3(NYX):c.70_93del (p.Arg24_Ala31del) variant on the X chromosome.

ClinVar: 99841

gnomAD: NM_001378477.3(NYX):c.70_93del (p.Arg24_Ala31del) has a maximum allele frequency of 0.0001018 (1/9823, with no males or homozygous females) in the European non-Finnish population https://gnomad.broadinstitute.org/variant/X-41332781-GGCCTGCGCCCGCGCTTGTCCCGCC-G

FamilyAddInfo: Family phenotypes were described in PMID: 2574143.

FamilyPMIDs: PMID: 2574143

PMID: 11062471

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

PMID: 12397430

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

PMID: 14507859

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

Selection A - Gene is expressed in tissues relevant to disease:

ExperimentName: Nyx localization to the post-synaptic side of both synaptic layers of the zebrafish retina

TissueExpression: UBERON:0001790 (Outer plexiform layer of retina), UBERON:0001795 (Inner plexiform layer of retina

ExpressionEvidence: Nyx was detected by antibody staining of zebrafish retinal sections and was found to localize strongly to both synaptic layers (the outer plexiform layer and inner plexiform layer) but not the outer nuclear layer or inner nuclear layer (Fig. 5A). Lack of co-localization between Nyx and either SV2 or PSD-95 (two presynaptic markers) confirmed that Nyx is specifically post-synaptically localized (Figs. 5C, 6A). This was further confirmed by the detection of Nyx-labeled second-order neuron dendrites invaginating into presynaptic cone pedicles (Figs. 6B and 6C). This data is highly compatible with the findings of a separate mouse experiment (PMID: 17881478) showing that Nyx transgene expression in the dendritic tips of retinal depolarizing bipolar cells rescues the phenotype of Nyx-deficient mice.

PMID: 17004930

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

PMID: 26072023

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

PMID: 16670814

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

PMID: 18617546

Gene: NYX

HGNC: 8082

Disease: Congenital stationary night blindness 1A

MONDO: 0010690

InheritancePattern: X-linked recessive

Prevalence: Congenital stationary night blindness has an estimated prevalence between 1 in 6,000 (PMID: 31427709) and 1 in 300,000 (PMID: 3487908). However, the prevalence of congenital stationary night blindness 1A specifically is unknown.

Penetrance: Penetrance is thought to be complete.

Case#: Leroy_2009_Family_A_Patient_III-14, male, age 58 years, family of Flemish ethnicity and Belgian national origin

CasePresentingHPOs: HP:0030640 (Complete congenital stationary night blindness), HP:0007663 (Reduced visual acuity), HP:0007984 (Electronegative electroretinogram), HP:0000639 (Nystagmus), HP:0003593 (Infantile onset), HP:0025404 (Abnormal visual fixation), HP:0000545 (Myopia), HP:0001104 (Macular hypoplasia), HP:0001417 (X-linked inheritance)

CaseHPOFreeText: N/A

CaseNotHPOs: HP:0000613 (Photophobia), HP:0030526 (Severe constriction of peripheral visual field), HP:0030602 (Abnormal fundus autofluorescence imaging), HP:0025158 (Hyperautofluorescent retinal lesion)

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

CaseMethod1: Sanger sequencing of PCR amplified exons from NYX

CaseMethod2: Haplotype analysis using microsatellite markers surrounding the NYX locus, in multiple apparently unrelated patients sharing the same variant

CaseGenotypingMethod: The proband and family members were subjected to Sanger sequencing of NYX to identify the variant, followed by haplotype analysis in comparison to apparently unrelated patients harboring the same variant.

Variant: The proband harbors the NM_022567.2:c.856del (p.Asp286ThrfsTer62) variant on the X chromosome.

CAID: CA2573050962

gnomAD: NM_022567.2:c.856del (p.Asp286ThrfsTer62) was not found in gnomAD.

VariantEvidence: The NM_022567.2:c.856del (p.Asp286ThrfsTer62) variant is located in exon 2/2 and is not predicted to trigger NMD. It is predicted to introduce a premature stop codon that would disrupt the C-terminal 41% of the protein product while adding 62 different amino acids.

CaseAddInfo: The proband comes from a large family with inheritance through an unaffected carrier mother and transmission to a grandson through an unaffected carrier daughter. This variant appears in 3 different families of Flemish Belgian origin, and is suspected to be a founder mutation in this population.

CasePMIDs: N/A