Oculocutaneous albinism (OCA) is genetically and clinically heterogeneous recessive disorders with at least 23 associated genes. Isolated OCA is characterized by hypopigmentation in the skin, hair, and eyes combined with ocular abnormalities. Hermansky Pudlak syndrome (HPS) and Chediak-Higaski syndrome are syndromic forms of OCA, distinguished by immunological and hematological symptoms in addition to hypopigmentation and ocular anomalies. Targeted clinical care is crucial for the patients and molecular genetic diagnosis is important for classification of patients. Current diagnostic yield is approximately 70%, and a high prevalence of patients, heterozygous for pathogenic variants in OCA genes, might suggest presence of disease-causing non-coding variants. We describe here NGS analysis, including CNV analysis, of 28 consanguineous families, comprising a total of 136 individuals presenting with OCA. We provide a molecular genetic diagnosis in all 28 families. Noteworthy, five families (18 %) had pathogenic variants in a gene associated with HPS. Furthermore, we report the first deep intron variant in TYR causing OCA and show by minigene analysis that the variant causes inclusion of a pseudoexon.

The authors have declared no competing interest.

This work was funded by the Novo Nordisk Foundation [NNF19OC0058469 to K.G] and [NNF19OC0058588 to B.S.A].

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The study followed the declaration of Helsinki and was approved by the Institutional Review Board of GC University Faisalabad, Faisalabad, Pakistan and Institutional Research Board (IRB), Health Services Academy (HSA), Islamabad, Pakistan.

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