Hermansky-Pudlak syndrome (HPS) is a heterogeneous disorder combining oculocutaneous albinism (OCA) and a platelet function disorder of varying severity as its most prominent
features. The genes associated with HPS encode for different BLOC- (biogenesis of lysosome-related
organelles complex) complexes and for the AP-3 (adaptor protein-3) complex, respectively. These
proteins are involved in maturation, trafficking, and the function of lysosome-related organelles
(LROs) such as melanosomes and platelet δ-granules. Some patients with different types of HPS
can develop additional complications and symptoms like pulmonary fibrosis, granulomatous colitis,
and immunodeficiency. A new type of HPS has recently been identified associated with genetic
alterations in the BLOC1S5 gene, which encodes the subunit Muted of the BLOC-1 complex. Our
aim was to unravel the genetic defect in two siblings with a suspected HPS diagnosis (because of
OCA and bleeding symptoms) using next generation sequencing (NGS). Platelet functional analysis
revealed reduced platelet aggregation after stimulation with ADP and a severe secretion defect in
platelet δ-granules. NGS identified a novel homozygous essential splice site variant in the BLOC1S5
gene present in both affected siblings who are descendants of a consanguine marriage. The patients
exhibited no additional symptoms. Our study confirms that pathogenic variants of BLOC1S5 cause
the recently described HPS type 11
