Table 3.
Potential contribution of TYR S192Y/R402Q haplotype to molecular diagnoses in OCA cohorts with missing heritability.
| Study | This studya | Oetting17 | Ghodsinejad Kalahroudi20 | Lasseaux22 | Gronskov31 | Campbell30 |
|---|---|---|---|---|---|---|
| Phenotype | Nystagmus and/or albinism | OCA1 | OCA1 | Nystagmus and/or absence of fovea | Albinism (OCA, AROA or OA) | Nystagmus and at least one other ocular feature of albinism, no skin hypopigmentation |
| Country (ethnicity) | England | NA | (Iranian) | France | Scandinavia (Scandinavian) | England |
| Number of individuals in the cohort | 51 | 3 | 6 | 158 | 29 | 4 |
| Number of individuals hom or het for both TYR S192Y and R402Q, where S192Y/R402Q haplotype is possible | 49 | 2 | 0 | 64 | 21 | 4 |
| Number of individuals in whom it was possible to determine the phase of TYR S192Y, R402Q and pathogenic or likely pathogenic variants (“informative cohort”) | 23 | 2 | 6 | 31 | 6 | 2 |
| Number of individuals in whom TYR S192Y and R402Q were in cis, and in trans to pathogenic or likely pathogenic TYR variant in the informative cohort | 23 | 2 | 0 | 31 | 6 | 2 |
| The proportion of “informative cohort” where S192Y/R402Q haplotype is possible and molecular diagnoses due to TYR S192Y/R402Q haplotype in trans to pathogenic or likely pathogenic TYR variant | 23/23 (100%) | 2/2 (100%) | S192Y/R402Q haplotype not possible in any individuals in the study | 31/31 (100%) | 6/6 (100%) | 2/2 (100%) |
| Combined proportion of “informative cohort” where molecular diagnoses are due to TYR S192Y/R402Q haplotype in trans to pathogenic or likely pathogenic TYR variant | 64/64 (100%) | |||||
| The proportion of cohort where molecular diagnoses due to TYR S192Y/R402Q haplotype in trans to pathogenic or likely pathogenic TYR variant | 23/51 (45.1%) | 2/3 (66.7%) | 0/6 (0%) | 31/158 (19.6%) | 6/29 (20.7%) | 2/4 (50%) |
| Combined proportion of cohort where molecular diagnoses are due to TYR S192Y/R402Q haplotype in trans to pathogenic or likely pathogenic TYR variant | 64/251 (25.5%) |
This includes individuals with only 1 TYR pathogenic or likely pathogenic variant identified.
AROA autosomal recessive ocular albinism, het heterozygous, hom homozygous, OCA oculocutaneous albinism, OA ocular albinism.
aThis cohort includes individuals previously reported in Norman et al. and O’Gorman et al.