Journal Article

Hermansky-Pudlak syndrome and oculocutaneous albinism in Chinese children with pigmentation defects and easy bruising

Power, Bradley, Ferreira, Carlos R., Stephen, Joshi, Malicdan, May Christine V., Chen, Dong, Zein, Wadih M., Introne, Wendy J., Adams, David R., O’Brien, Kevin J., Huizing, Marjan, Gochuico, Bernadette R., Gahl, William A.

2019

Overview

Background Determining the etiology of oculocutaneous albinism is important for proper clinical management and to determine prognosis. The purpose of this study was to genotype and phenotype eight adopted Chinese children who presented with oculocutaneous albinism and easy bruisability. Results The patients were evaluated at a single center; their ages ranged from 3 to 8 years. Whole exome or direct sequencing showed that two of the children had Hermansky-Pudlak syndrome (HPS) type-1 (HPS-1), one had HPS-3, one had HPS-4, and four had non-syndromic oculocutaneous albinism associated with TYR variants (OCA1). Two frameshift variants in HPS1 (c.9delC and c.1477delA) , one nonsense in HPS4 (c.416G > A), and one missense variant in TYR (c.1235C > T) were unreported. The child with HPS-4 is the first case with this subtype reported in the Chinese population. Hypopigmentation in patients with HPS was mild compared to that in OCA1 cases, who had severe pigment defects. Bruises, which may be more visible in patients with hypopigmentation, were found in all cases with either HPS or OCA1. Whole mount transmission electron microscopy demonstrated absent platelet dense granules in the HPS cases; up to 1.9 mean dense granules per platelet were found in those with OCA1. Platelet aggregation studies in OCA1 cases were inconclusive. Conclusions Clinical manifestations of oculocutaneous albinism and easy bruisability may be observed in children with HPS or OCA1. Establishing definitive diagnoses in children presenting with these phenotypic features is facilitated by genetic testing. Non-syndromic oculocutaneous albinism and various HPS subtypes, including HPS-4, are found in children of Chinese ancestry.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Albinism / Albinism, Oculocutaneous - diagnosis / Albinism, Oculocutaneous - etiology / Albinism, Oculocutaneous - genetics / Analysis / Blood Platelets - metabolism / Blood Platelets - pathology / Bruising / Care and treatment / Child / Child health / Child, Preschool / Children / Chinese / Clinical genetics and genomics / Defects / Dense granule / Diagnosis / Electron microscopy / Etiology / Etiology (Medicine) / Female / Genetic screening / Genetic testing / Genotype / Genotypes / Hermanski-Pudlak Syndrome - diagnosis / Hermanski-Pudlak Syndrome - etiology / Hermanski-Pudlak Syndrome - genetics / Hermansky-Pudlak syndrome / Human Genetics / Humans / Hypopigmentation / Laboratories / Lung diseases / Male / Medical research / Medicine / Medicine & Public Health / Microscopy / Microscopy, Electron, Transmission / Mutation / Mutation - genetics / Neutropenia / Oculocutaneous albinism / Patients / Pedigree / Pharmacology/Toxicology / Phenotypes / Pigmentation / Pigmentation disorders / Platelet aggregation / Population / Prognosis / Pulmonary fibrosis / Rare diseases / Transmission electron microscopy / Transplants & implants