In the index patient (IV1) of family OA1-3 that did not show exon deletion, sequence analysis of all coding exons including the exon-intron boundaries revealed a deletion of a single nucleotide G at position 310 of the cDNA introducing a subsequent premature stop codon one codon downstream, predicting a deleterious protein product. This newly described mutation (310delG) in exon 2 of the OA1 gene creates a TaqI restriction site. Although the pedigree of family OAI-3 initially suggested the patient IV1 to be a sporadic case, PCR-restriction analysis identified the patient's maternal uncle (III3), known to have only a decreased visual acuity at age 38, as hemizygous for the mutation. The mother (III2) and the maternal grand-mother (II1) of the proband were found to be carriers (Fig. (Fig.4B),4B), as expected
Case#: Faugere_2003_Family_OA1-3_Patient_IV1, male, 26 years of age at time of report, family origin reported to be from the South of France with race described as Caucasian
CasePresentingHPOs: HP:0006934 (Congenital nystagmus), HP:0007750 (Hypoplasia of the fovea), HP:0007663 (Reduced visual acuity), HP:0001089 (Iris atrophy), HP:0012805 (Iris transillumination defect), HP:0007894 (Hypopigmentation of the fundus), HP:0030602 (Abnormal fundus autofluorescence imaging), HP:0030479 (Abnormal amplitude of light-adapted flicker electroretinogram)
CaseHPOFreeText: The proband was initially diagnosed with congenital nystagmus.
CaseNotHPOs: HP:0012632 (Abnormal intraocular pressure), HP:0000518 (Cataract)
CaseNotHPOFreeText: N/A
CasePreviousTesting: Previous testing was not described, however, the proband was examined for whole-exon deletions using PCR amplification of the 9 exons from the GPR143 locus.
CaseMethod1: Sanger sequencing
CaseMethod2: Restriction enzyme analysis using TaqI
CaseGenotypingMethod: The proband was examined for whole-exon deletions using PCR amplification of the 9 exons from the GPR143 locus, followed by Sanger-based sequencing and restriction enzyme-based screening of family members using TaqI.
Variant: The proband harbors the NM_000273.3(GPR143):c.310del (p.Asp104fs) variant in the hemizygous state.
ClinVar: 98625
gnomAD: This variant was not found in gnomAD v2.1.1.
VariantEvidence: NM_000273.3(GPR143):c.310del (p.Asp104fs) is a frameshift variant in exon 2 of 9, and is predicted to trigger nonsense-mediated decay or to at least truncate the C-terminal 75% of the protein product.
CaseAddInfo: While the proband was initially thought to be a sporadic case, the variant was later found to be maternally inherited, with an uncle found to harbor the variant and to be affected with decreased visual acuity. Further details of the family member are not described.
CasePMIDs: N/A