Case#: Zeitz_2006_Family_A_II-5, male, onset in early childhood, family ancestry reported as Swiss
CasePresentingHPOs: HP:0011463 (Childhood onset), HP:0000639 (Nystagmus), HP:0007663 (Reduced visual acuity), HP:0000613 (Photophobia)
CaseHPOFreeText: The proband and his sibling have diagnosis of congenital stationary night blindness, in the absence of family history of the disease. BCVA was 20/100 at age 15 years. Disease course was stationary for 30 years but later included a decrease in visual acuity and development of moderate photophobia.
CaseNotHPOs: HP:0000662 (Nyctalopia)
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous genotyping was limited to Sanger sequencing of PCR products from the CACNA1F gene. The authors also implied that similarly screening was performed all other known genes associated CSNB, which at the time included RHO, GNAT1, PDE6B, GRK1, SAG, NYX, and GRM6.
CaseMethod1: Sanger sequencing of CABP4
CaseMethod2: N/A
CaseGenotypingMethod: Genotyping was limited to Sanger sequencing of PCR products from the CACNA1F and CABP4 genes, with possible sequencing of other known CSNB-associated genes RHO, GNAT1, PDE6B, GRK1, SAG, NYX, and GRM6.
Variant: The individual harbors the NM_145200.3(CABP4):c.800_801delAG variant in the homozygous state.
ClinVar ID: 1952
gnomAD: The variant is found in gnomAD version 4.1.1 at a frequency of 0.00007043 in the European (non-Finnish) population, with 0 homozygotes
https://gnomad.broadinstitute.org/variant/11-67226099-CAG-C?dataset=gnomad_r2_1
VariantEvidence: NM_145200.3(CABP4):c.800_801delAG is a frameshift variant within exon 6 of 6 that is predicted not to trigger nonsense-mediated decay but rather to disrupt the C-terminal 9 amino acids (3%) of the protein product and to extend the remaining protein by 91 additional amino acids. Analysis of patient mRNA indicates that splicing occurs normally but that expression at the mRNA level is decreased by more than 50% relative to the unaffected family member control.
CaseAddInfo: The proband's family is reportedly non-consanguineous, and includes a similarly affected brother who is also homozygous for the variant, as well as unaffected parents and 4 unaffected siblings who are heterozygous or lacking the variant (Figure 2A). Family history was negative for CSNB.
CasePMIDs: N/A