New Deletions in the Hermansky-Pudlak Syndrome Type 5 Gene in a Japanese Patient

Shinya Kato,Tsugumi Aoe,Akie Hamamoto,Hiroshi Takemori,Toshiya Nishikubo

doi:10.3390/reports2020015

Abstract

The Hermansky-Pudlak syndrome (HPS) is a rare disease characterized by oculocutaneous albinism and prolonged bleeding. HPS is caused by alterations in HPS1-10 and their related genes, comprising the biogenesis of lysosome-related organelles complex 1–3 and adapter protein 3. Here, we report a Japanese patient with HPS associated with mild hypopigmentation, nystagmus, and impaired visual acuity. Sequencing analyses of the mRNA of this patient revealed new deletions (ΔGA and ΔG) in the HPS5 gene. This was the first case of HPS5 gene deficiency in Japan, and the two above-mentioned deletions have not yet been reported among patients with HPS5.

Highlights

The Hermansky-Pudlak syndrome (HPS) was first reported in 1959, when two patients with oculocutaneous albinism, prolonged bleeding, and pigmented macrophages in the bone marrow were identified and their symptoms were described [1]
BLOC-1 is a multimeric complex, composed of HPS7, HPS8, and HPS9 [9]; BLOC-2 is composed of HPS3, HPS5, and HPS6 [10]; and BLOC-3 is composed of HPS1 and HPS4 [11]
When we examined the sequences of the 50 regions of HPS3, HPS5, and HPS6 genes, we found error peaks of nucleotides in the HPS5 gene, suggesting the presence of deletions or insertions

Summary

Introduction

The Hermansky-Pudlak syndrome (HPS) was first reported in 1959, when two patients with oculocutaneous albinism, prolonged bleeding, and pigmented macrophages in the bone marrow were identified and their symptoms were described [1]. After the amplification of the HPS-5 gene fragments by PCR, variants were detected by direct sequencing (B) or after sub-cloning into plasmid vectors (C). Delta granules primarily contained calcium, ATP, amplified cDNAs by reverse transcriptase-polymerase chain reaction, RT-PCR, and determined the sequences of coding regions for HPS-related genes, by direct sequencing. WBC—white blood cell, RBC—red blood cell, HGB—hemoglobin, HCT—hematocrit, MCV—mean corpuscular volume, MCH—mean corpuscular hemoglobin, MCHC—mean corpuscular hemoglobin concentration, PT—prothrombin time, PT-INR—prothrombin time international normalized ratio, AP—active prothrombin, APTT—activated partial thromboplastin time, FDP—fibrin degradation products, AST—aspartate aminotransferase, ALT—alanine aminotransferase, LDH—lactate dehydrogenase, ALP—alkaline phosphatase, γ-GTP—gamma glutamyl transpeptidase, TP—total protein, ALB—albumin, Ch-E—cholinesterase, BUN—blood urea nitrogen, CRE—creatinine, CK—creatine kinase, UA—uric acid, T-CHO—total cholesterol, TG—triglycerides, T-Bil—total bilirubin, DB—direct bilirubin, IB—indirect bilirubin, Na—sodium, K—potassium, Cl—chloride, Ca—calcium, Fe—ferrum, TIBC—total iron binding capacity, UIBC—unsaturated iron binding capacity, CRP—C-reactive protein, eGFR—estimate glomerular filtration rate, L—low, H—high. By amplifying the whole coding region using a long PCR, followed by sub-cloning into a plasmid vector, we confirmed that these deletions were on the individual alleles (Figure 1C)

Discussion

Conclusions