Genetic and phenotypic analysis of Hermansky-Pudlak syndrome type 6 family with a special platelet phenotype
10.3760/cma.j.cn511434-20241028-00397
- VernacularTitle:一种特殊血小板表型的Hermansky-Pudlak综合征6型家系基因与表型分析
- Author:
Zhongqiang ZHOU
1
;
Pingling SHI
1
;
Haiying PENG
1
;
Qian LI
1
;
He TANG
1
;
Yuanmeng WEI
1
Author Information
1. 河南省人民医院 郑州大学人民医院 河南省立眼科医院, 郑州 450003
- Publication Type:Journal Article
- Keywords:
Hermansky-Pudlak syndrome;
Clinical manifestation;
Genetic characteristics;
Platelet dense granules
- From:
Chinese Journal of Ocular Fundus Diseases
2025;41(9):690-696
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To identify and observe the pathogenic genes and clinical phenotypes of a family with a special platelet phenotype, Hermansky-Pudlak syndrome type 6 (HSP6).Methods:A retrospective clinical study. In November 2019, one proband and three family members from six HSP families who visited Henan Eye Hospital were included in the study. The child's medical history and family history were inquired in detail. The proband and all family members underwent best corrected visual acuity (BCVA), fundus color photography, frequency-domain optical coherence tomography, and general physical examination. The proband underwent platelet transmission electron microscopy (PTEM) and colonoscopy. Peripheral venous blood was collected from the proband, her parents and younger brother, and genomic DNA was extracted. Whole exome sequencing (WES) was used to screen pathogenic genes and their loci. Bioinformatics analysis determines the pathogenicity of gene variation sites. Fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to verify the related variations.Results:The proband (Ⅱ-1) was a 7-year-old female. The BCVA in both eyes was 0.1, who exhibited mild horizontal nystagmus and iris depigmentation. Fundus examination revealed obvious depigmentation and an underdeveloped fovea centralis. At the age of 7, the patient underwent colonoscopy due to acute gastrointestinal bleeding. A polyp approximately 5 mm in size was found on the floor of the sigmoid colon, with erosion and mucosal leukoplakia on its surface. PTEM showed that the number of platelet dense granules was normal, but the nuclei were small or exhibited low compactness. The skin on both lower legs showed pigmentation. The clinical phenotypes of the proband’s parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) showed no obvious abnormalities. WES revealed that the proband carried compound heterozygous variants in exon 1 of the HPS6 gene: c.60_64dup (p.L22fs) (M1) and c.1147_1148del (p.L383fs) (M2). The mother carried the M1 variant, while the father and younger brother carried the M2 variant. Bioinformatics analysis predicted that both variants were pathogenic. RT-qPCR results showed that, compared with the relative expression level of HPS6 wt mRNA, the relative expression levels of HPS6 L22fs and HPS6 L383fs mRNA were significantly decreased ( t = 3.549, 4.560; P<0.05). Western blot analysis demonstrated that the HPS6 L383fs protein was truncated, whereas the HPS6 L22fs protein was not detected. Conclusions:This family is a special HPS6 with a normal number of dense platelet granules. The compound heterozygous variations of M1 and M2 in the HPS6 gene are pathogenic genes in this family.
