Diagnosis of a case with Hermansky-Pudlak syndrome type 5 through high-throughput sequencing and a literature review
王东 1黄静 2张开慧 1律玉强 1高敏 1马健 1宛雅 1盖中涛 1刘毅 1鞠翠钰
扫码查看
点击上方二维码区域，可以放大扫码查看
作者信息
1. 1山东大学附属儿童医院儿科研究所，济南 250022
2. 2山东大学附属儿童医院眼科，济南 250022
折叠
摘要
目的 探讨Hermansky-Pudlak综合征5型(HPS-5)患者的临床和遗传学特征。 方法 选取2019年10月3日于山东大学附属儿童医院就诊的1例HPS-5患儿为研究对象。收集患儿相关临床资料，应用高通量测序技术对该患儿进行基因变异分析，并进行文献复习。 结果 患儿为1岁5个月女孩，临床表现为自幼眼球震颤，眼底检查发现视网膜大部分色素脱失，易瘀伤。高通量测序结果提示患儿携带HPS5基因复合杂合变异：c.1562_1563delAA(p.F521Sfs*27)和c.1404C>A(p.C468X)，分别遗传自其父亲与母亲。根据美国医学遗传学与基因组学学会(ACMG)相关指南，该两个变异均判定为致病性变异(PVS+PM2_Supporting+PM3+PP4)。已报道的18例HPS-5患者均有眼部问题，大多数有出血倾向；8例携带HPS5基因复合杂合变异，8例携带纯合变异，2例携带双纯合变异，大多数变异为无效变异。 结论 本研究患儿为HPS5基因变异所致HPS-5患者，高通量测序分析为疾病的诊断提供了重要工具。HSP-5患者通常具有典型眼白化病或眼皮肤白化病及出血倾向的临床表现，严重并发症较少，以HPS5基因复合杂合变异和纯合变异为主。 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 theHPS5 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 theHPS5 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.
Abstract
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 theHPS5 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 theHPS5 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.
关键词
眼白化病/Hermansky-Pudlak综合征5型/HPS5基因/高通量测序
Key words
Ocular albinism/Hermansky-Pudlak syndrome type 5/HPS5 gene/High-throughput sequencing
万方数据