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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

To characterize the phenotype and genotype of a syndrome associating posterior microphthalmos (PM), retinitis pigmentosa (RP), foveoschisis, and foveal hypoplasia (FH) in a consanguineous Portuguese family. Three siblings were studied and underwent comprehensive eye examinations for best-corrected visual acuity, axial length, refractive error, B-mode ultrasound, electroretinography, retinography, fluorescein angiography (FA), kinetic visual field (VF), and optical coherence tomography (OCT). Molecular analysis was performed by Sanger sequencing of the entire coding region of the MFRP gene. All members presented nyctalopia, decreased visual acuity, and constriction of the VF, as well as bilateral shortening of the posterior ocular segment and normal anterior segment dimensions. The fundoscopy and ERG results were compatible with RP. Macular OCT analysis revealed schisis of the outer retinal layer, FH, as well as retinal and choroidal folds. We identified a homozygous mutation in intron 9 of the membrane frizzled-related protein (MFRP) gene (c.1124 + 1 G > A). Our study shows a family with PM and RP due to a mutation in the MFRP gene. The relationship has previously been proven, but this specific mutation has never been described. These gene mutations show wide phenotypic variability, being evident in the presence of foveoschisis, retinal and choroidal folds, and FH, other than PM and RP. [ABSTRACT FROM AUTHOR]