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Background <p>Hermansky-Pudlak Syndrome (<i>HPS</i>) is a rare autosomal recessive syndromic type of albinism. It is characterized by oculocutaneous hypopigmentation, platelet dysfunction, and variable systemic involvement depending on the specific subtype. To date, eleven distinct <i>HPS</i> types have been identified, with <i>HPS3</i> being among the milder forms.</p> Methods and results <p>Clinical and ophthalmic examinations, followed by whole exome sequencing (WES), Sanger sequencing, and segregation analysis, were performed. Here, we report a case of a 26-year-old Lebanese male patient born to consanguineous parents who presented with oculocutaneous albinism without a history of bleeding or other systemic involvement. WES identified a novel homozygous nonsense variant in the <i>HPS3</i> gene (NM_032383.5): c.998T &gt; A; p.(Leu333Ter) that co-segregated with the phenotype. The platelet function analysis (PFA-100) revealed a prolonged collagen/epinephrine closure time, accompanied by a normal collagen/ADP response.</p> Conclusions <p>We report one of the very few <i>HPS3</i> cases in the Middle East and North Africa region (MENA) and the Arab regions, caused by a novel homozygous nonsense variant associated with platelet dysfunction. In contrast to the founder mutations described in Puerto Rican and Ashkenazi Jewish populations, HPS3 cases in this region appear to result from distinct mutational events, indicating the absence of a common ancestral origin.</p>

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A novel HPS3 pathogenic nonsense variant associated with Hermansky-Pudlak syndrome type 3 and a platelet dysfunction

  • 期刊论文

  • 发表日期：

    2025年11月6日

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  • Chahnaz Chouman,
  • Suzana Salhab,
  • Salvatore Martella,
  • Zahraa Mousawi,
  • Alexandre Assi,
  • Alain Chebly,
  • Said El Shamieh

摘要

Background

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive syndromic type of albinism. It is characterized by oculocutaneous hypopigmentation, platelet dysfunction, and variable systemic involvement depending on the specific subtype. To date, eleven distinct HPS types have been identified, with HPS3 being among the milder forms.

Methods and results

Clinical and ophthalmic examinations, followed by whole exome sequencing (WES), Sanger sequencing, and segregation analysis, were performed. Here, we report a case of a 26-year-old Lebanese male patient born to consanguineous parents who presented with oculocutaneous albinism without a history of bleeding or other systemic involvement. WES identified a novel homozygous nonsense variant in the HPS3 gene (NM_032383.5): c.998T > A; p.(Leu333Ter) that co-segregated with the phenotype. The platelet function analysis (PFA-100) revealed a prolonged collagen/epinephrine closure time, accompanied by a normal collagen/ADP response.

Conclusions

We report one of the very few HPS3 cases in the Middle East and North Africa region (MENA) and the Arab regions, caused by a novel homozygous nonsense variant associated with platelet dysfunction. In contrast to the founder mutations described in Puerto Rican and Ashkenazi Jewish populations, HPS3 cases in this region appear to result from distinct mutational events, indicating the absence of a common ancestral origin.