Unraveling Hermansky–Pudlak syndrome type 7: a case report and comprehensive literature review on the identification of DTNBP1 variants

ABSTRACT

Purpose

We report a case of Hermansky–Pudlak Syndrome type 7 (HPS-7) caused by a homozygous variant in the dystrobrevin-binding protein 1 gene (DTNBP1) and highlight the genetic challenges associated with this rare disorder.

Methods

Case report. Literature review was performed by searching PubMed on May 2023, without language or date restriction, using the following terms: Hermansky–Pudlak syndrome, Hermansky–Pudlak syndrome type 7, and dystrobrevin-binding protein 1 gene.

Results

We report a case of a 69-year-old Portuguese female who presented for ophthalmic evaluation with long-standing severe visual impairment, pronounced photophobia, right-eye esotropia, and bilateral pendular nystagmus. Anterior segment examination revealed iris transillumination defects, while the ocular fundus showed hypopigmentation and the absence of the foveal reflex. The patient had a history of oculocutaneous albinism (OCA) and recurrent epistaxis. Her family history was positive for first-degree consanguineous parents and a deceased sister at young age who also exhibited OCA and recurrent epistaxis. Genetic testing identified a homozygous pathogenic nonsense variant in the DTNBP1, c.307C>T p.(Gln103*). The patient’s clinical features and genetic testing support the diagnosis of HPS-7. The identified variant has been previously reported in the literature, in adult patients of Portuguese descent.

Conclusion

This work highlights the genetic complexity of HPS-7 and emphasizes the importance of genetic testing in the diagnosis of this rare disorder. The identification of a rare pathogenic variant expands our understanding of HPS-7 genetics and suggests a possible founder effect in the Portuguese population.

KEYWORDS:

• Hermansky–Pudlak syndrome
• Hermansky–Pudlak syndrome type 7
• oculocutaneous albinism
• bleeding diathesis
• dystrobrevin-binding protein 1 gene
• dysbindin
• biogenesis of lysosome-related organelle complex

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article..

Additional information

Funding

This work was not supported by any funding.