Diagnostic Yield of Genetic Testing for Ocular and Oculocutaneous Albinism in a Diverse United States Pediatric Population

Genes (Basel). 2023 Jan 3;14(1):135. doi: 10.3390/genes14010135.

Abstract

The diagnostic yield of genetic testing for ocular/oculocutaneous albinism (OA/OCA) in a diverse pediatric population in the United States (U.S.) is unclear. Phenotypes of 53 patients who presented between 2006-2022 with OA/OCA were retrospectively correlated with genetic testing results. Genetic diagnostic yield was defined as detection of pathogenic/likely pathogenic variant(s) matching the anticipated inheritance for that gene-disease relationship. Variant reclassifications of those with variants of uncertain significance (VUS) and without positive diagnostic yield were completed. Overall initial genetic diagnostic yield of OA/OCA was 66%. There was no significant difference (p = 0.59) between race and ethnicities (Black (78%), White (59%), Hispanic/Latino (64%)); however, the diagnostic yield of OA (33%) was significantly lower (p = 0.007) than OCA (76%). Causative variants in OCA2 (28%) and TYR (20%) were most common. Further, Hermansky-Pudlak syndrome variants were identified in 9% of patients. Re-classification of VUS in non-diagnostic cases resulted in genetic diagnoses for 29% of individuals and increased overall diagnostic yield to 70% of all subjects. There is a high diagnostic yield of genetic testing of patients overall with OA/OCA in a diverse U.S. based pediatric population. Presence or absence of cutaneous involvement of albinism significantly affects genetic diagnostic yield.

Keywords: diagnostic yield; ocular albinism; oculocutaneous albinism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albinism, Ocular* / genetics
  • Child
  • Genetic Testing
  • Hermanski-Pudlak Syndrome* / genetics
  • Humans
  • Membrane Transport Proteins / genetics
  • Mutation
  • Retrospective Studies

Substances

  • Membrane Transport Proteins

Grants and funding

This research was supported by a 2022 Illinois Society for the Prevention of Blindness research grant to Kyle Chan (mentor Jennifer Rossen, MD).