Novel variants in the BLOC1S3 gene in patients presenting a mild form of Hermansky-Pudlak syndrome.

ABSTRACT

Hermansky-Pudlak syndrome (HPS) associates oculocutaneous albinism and systemic affections including platelet dense granules anomalies leading to bleeding diathesis and, depending on the form, pulmonary fibrosis, immunodeficiency, and/or granulomatous colitis. So far, 11 forms of autosomal recessive HPS caused by pathogenic variants in 11 different genes have been reported. We describe three HPS-8 consanguineous families with different homozygous pathogenic variants in BLOC1S3 (NM_212550.3), one of which is novel. These comprise two deletions leading to a reading frameshift (c.385_403del, c.338_341del) and one in frame deletion (c.444_467del). All patients have moderate oculocutaneous albinism and bleeding diathesis, but other HPS symptoms are not described. One patient diagnosed with HPS-8 suffered from lymphocyte-predominant Hodgkin lymphoma. The mild severity of HPS-8 is consistent with other HPS forms caused by variants in BLOC-1 complex coding genes (HPS-7, DTNBP1; HPS-9, BLOC1S6, HPS-11, BLOC1S5).