OBJECTIVE: To explore the clinical and genetic characteristics of a patient with Hermansky-Pudlak syndrome type 5 (HPS-5). METHODS: A child with HPS-5 who had attended the Children's Hospital Affiliated to Shandong University on October 3, 2019 was selected as the study subject. Clinical data of the child were collected. Genetic variant was analyzed through high-throughput sequencing. A literature review was also carried out. RESULTS: The child, a 1-year-and-5-month-old girl, had nystagmus since childhood, lost of retinal pigmentation by fundus examination and easy bruising. High-throughput sequencing revealed that she has harbored compound heterozygous variants of the HPS5 gene, namely c.1562_1563delAA (p.F521Sfs*27) and c.1404C>A (p.C468X), which were inherited from his father and mother, respectively. Based on the guidelines from the American College for Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS+PM2_Supporting+PM3+PP4). Among 18 previously reported HPS-5 patients, all had had eye problems, and most of them had tendency for bleeding. Eight cases had carried compound heterozygous variants of the HPS5 gene, 8 carried homozygous variants, 2 carried double homozygous variants, and most of them were null mutations. CONCLUSION The c.1562_1563delAA(p.F521Sfs*27) and c.1404C>A (p.C468X) compound heterozygous variants of the HPS5 gene probably underlay the HPS-5 in this child. High-throughput sequencing has provided an important tool for the diagnosis. HSP-5 patients usually have typical ocular albinism and/or oculocutaneous albinism and tendency of bleeding, which are commonly caused by compound heterozygous and homozygous variants of the HPS5 gene, though serious complications have been rare.
Female ; Humans ; Infant ; Hermanski-Pudlak Syndrome/pathology* ; High-Throughput Nucleotide Sequencing ; Mutation

Hermanski-Pudlak Syndrome ; complications ; Humans ; Immunologic Deficiency Syndromes ; complications ; Male ; Middle Aged ; Red-Cell Aplasia, Pure ; complications

OBJECTIVETo identify the mutations of the tyrosinase gene (TYR) and P gene in patients with oculocutaneous albinism (OCA).

METHODSPolymerase chain reaction (PCR) and denaturing high performance liquid chromatography (DHPLC) were applied to detect the mutations in all exons of TYR gene and P gene. Then DNA sequencing and restriction endonuclease analysis were used to confirm the mutations detected by DHPLC. Novel mutations were screened in 100 unrelated persons with normal phenotypes to exclude the possibility of polymorphism.

RESULTSTwo mutations were detected in the P gene of the three patients and none in TYR gene. Heterozygous mutation of T450M in exon 13 of the P gene was detected in patient 1. Patient 2 had a heterozygous mutation of T450M in exon 13 and a heterozygous mutation of G775R in exon 23 of the P gene. Patient 3 had a heterozygous mutation of G775R as well. Restriction endonuclease analysis of the P gene exon 13 showed that the Oli I site had partly disappeared resulting from the heterozygous mutation T450M in patient 1 and patient 2, but not in 100 unrelated individuals. The heterozygous mutation T450M is a novel mutation.

CONCLUSIONGene diagnosis of OCA can be carried out effectively by combining PCR, DHPLC, DNA sequencing and restriction endonuclease analysis.

Albinism, Oculocutaneous ; genetics ; Base Sequence ; Catechol Oxidase ; genetics ; Child, Preschool ; DNA Mutational Analysis ; Exons ; genetics ; Female ; Hermanski-Pudlak Syndrome ; genetics ; Humans ; Monophenol Monooxygenase ; genetics ; Mutation ; Young Adult

Alpha-storage pool deficiency of platelet is a very rare disorder associated with a variety of conditions, including autoimmune disease, disseminated intravascular coagulation, myeloproliferative disorders, and cardiopulmonary bypass. This bleeding disorder is characterized by a moderate thrombocytopenia and a selective abnormality in platelet alpha-granules. We experienced the first case of alpha-storage pool deficiency of platelet in a 28-year-old male with severe valvular heart disease in Republic of Korea. Two years ago, mitral valve replacement was performed in other university hospital. Since a few months ago, dyspnea was developed and progressively exacerbated. Transesophageal echocardiogram showed severe mitral valve regurgitation and aortic valve regurgitation. He had moderate thrombocytopenia. Bleeding time was prolonged. Peripheral blood smear showed hypogranular platelets with indistinct cell membrane. In bone marrow biopsy, there showed evidence of mild hyperplasia of megakaryocytes. Platelet aggregation test revealed abnormal response to collagen and epinephrine. Electron microscopy of periphral blood showed the vacuolization of alpha- granules of platelets. Following platelet transfusion, double valve replacement could be performed successfully. Six months later, platelet morphology was moderately normalized. But bleeding time and platelet aggregation test were still abnormal.
Adult ; Aortic Valve ; Autoimmune Diseases ; Biopsy ; Bleeding Time ; Blood Platelets* ; Bone Marrow ; Cardiopulmonary Bypass ; Cell Membrane ; Collagen ; Disseminated Intravascular Coagulation ; Dyspnea ; Epinephrine ; Heart Valve Diseases* ; Hemorrhage ; Humans ; Hyperplasia ; Male ; Megakaryocytes ; Microscopy, Electron ; Mitral Valve ; Mitral Valve Insufficiency ; Myeloproliferative Disorders ; Platelet Aggregation ; Platelet Storage Pool Deficiency ; Platelet Transfusion ; Republic of Korea ; Thrombocytopenia