A novel likely pathogenic variant in a patient with Hermansky-Pudlak syndrome.
Cold Spring Harb Mol Case Stud
; 7(5)2021 10.
Article
em En
| MEDLINE
| ID: mdl-34362826
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Hermanski-Pudlak
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Cold Spring Harb Mol Case Stud
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos