RP19
Family#: RP19
PresentingHPOs: HP:0007642, HP:0030824 (Congenital stationary night blindness, Mizuo-Nakamura phenomenon)
PresentingHPOsFreeText: Diffuse gray discoloration of the fundus, scotopic ERG showed a significantly reduced rod response (in selected individuals analyzed)
FamilyNotHPOsFreeText: During fundoscopy of the individuals IV-3 and V-1, no bone spicule deposits were observed in the fundus.
CountryOrigin: Pakistan, central region of Punjab province
Family#PreviousTesting: None
Family#Method1: Homozygosity mapping
Family#Method2: Sequencing
Family#GenotypingMethod: Linkage: Six affected family members were analyzed by whole-genome SNP analysis, which showed homozygosity for a 15.2 Mb region on chromosome 13q34. Using fluorescently labeled microsatellite markers to analyze all available family members, the critical region was refined to a 5-Mb region between D13S1315 (position 109.1 Mb) at the centromeric side and 13qter (position 114.1 Mb). All eight affected individuals were homozygous for this chromosomal interval (Figure 1). A maximum two-point LOD score of 5.1 for marker D13S1295 at theta 0 was determined.
All seven coding exons and flanking intronic sequences of GRK1 were sequenced in affected family members IV-1, V-5, and V-11. The segregation of a novel mutation in the family and the frequency of the identified mutation in the Pakistani population were determined by StuI RFLP analysis.
Affected: 8
Unaffected: 14
PublishedLOD: Maximum two-point LOD score of 5.1 for marker D13S1295 at theta 0.
ProbandLabel: RP19, IV-1
Variant: NM_002929.3(GRK1):c.614C>A (p.Ser205Ter) (homozygous)
ClinVar: 870430
CAID: CA388824706
gnomAD: Not in gnomAD
FamilyAddInfo: All parents, as well as several unaffected siblings, were heterozygous carriers of the variant. Eight unaffected individuals were homozygous for the wild-type sequence. In two branches of the family, (IV6/IV7, IV8/IV9, and their children) the parents are first cousins.