Novel variants in the <i>BLOC1S3</i> gene in patients presenting a mild form of Hermansky–Pudlak syndrome
Perrine Pennamen, Angèle Tingaud‐Sequeira, Vincent Michaud, Fanny Morice‐Picard, Claudio Plaisant, Catherine Vincent‐Delorme, Fabienne Giuliano, Saba Azarnoush, Yline Capri, Carolina Reato Marçon, Didier Lacombe, Eulalie Lasseaux, Benoı̂t Arveiler
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).