Document Type

Article

Publication Date

10-19-2021

Identifier

DOI: 10.1101/mcs.a006110

Abstract

Hermansky-Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism and variable pulmonary fibrosis, granulomatous colitis, or immunodeficiency. The diagnosis relies on clinical findings, platelet transmission electron microscopy studies showing absent dense granules, or the identification of a pathogenic genotype in one of 11 associated genes, including HPS1 We report a 2-wk-old male with significant iris transillumination defects, a pale fundus, and mild corectopia found by clinical exome sequencing to have a previously reported pathogenic variant, c.972dupC p.(Met325HisfsTer128), and a variant of uncertain significance, c.1846G>A p.(Glu616Lys), in HPS1 To determine whether his phenotype was consistent with HPS, follow-up studies of whole blood lumiaggregometry and platelet transmission electron microscopy were performed that revealed absent or markedly reduced platelet ATP secretion and virtually absent platelet dense granules, thus confirming the diagnosis. To the best of our knowledge, our case is the first in which the c.1846G>A p.(Glu616Lys) variant is identified in a patient with HPS. In addition, the case also highlights the importance of leveraging appropriate confirmatory clinical testing and reverse phenotyping, which allowed the care team to establish the clinical diagnosis of HPS and reclassify the previously reported variant of uncertain significance in HPS1 to likely pathogenic.

Journal Title

Cold Spring Harb Mol Case Stud

Volume

7

Issue

5

Keywords

abnormal number of dense granules; iris transillumination defect

Comments

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial License, which permits reuse and redistribution, except for commercial purposes, provided that the original author and source are credited.

Publisher's Link: http://molecularcasestudies.cshlp.org/content/7/5/a006110.long

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