目的:本研究旨在探讨临床特征,致病基因变异,中国遗传性球形红细胞增多症(HS)患者的潜在基因型-表型相关性。
方法:对江西省儿童医院诊断为HS患者的临床资料和分子遗传学特征进行回顾性分析。南昌大学第二附属医院,2017年11月至2023年6月,萍乡市人民医院、景德镇市第三人民医院。进行统计分析以比较和分析红细胞(RBC),血红蛋白(HB),平均红细胞体积(MCV),平均红细胞血红蛋白(MCH),以及基于不同突变和年龄组(<14岁和≥14岁)的组间和组内的平均红细胞血红蛋白浓度(MCHC)数据。
结果:本研究共纳入34例HS患者,包括22名儿童(64.70%)和12名成人(35.30%)。接受基因检测的先证者来自34个不相关的家庭。测试了32个变体,其中9个是新颖的。18例有ANK1变异,15个有SPTB变体,1具有SLC4A1变体。25名患者进行了核心家庭成员的基因检测,17(68.0%,17/25)是从头,5(20.0%,5/25)是母系遗传的,和3(12.0%,3/25)是父系遗传。与SPTB-HS患者相比,ANK1-HS患者表现出更严重的贫血,显示较低水平的红细胞和HB(P<0.05)。儿童期诊断的患者贫血比成年期诊断的患者更为严重。在ANK1-HS组中,成人患者MCH水平明显高于儿童(P<0.05),虽然红细胞没有显著差异,HB,MCV,两组间MCHC水平。患有SPTB-HS的成年患者的RBC水平明显较高,HB,MCH优于儿科患者(P<0.05),MCV和MCHC水平无显著统计学差异。
结论:本研究对诊断为HS的成人和儿童患者的表型特征和分子遗传学进行了比较分析。证实与SPTB-HS患者相比,小儿ANK1-HS患者表现出更严重的贫血表型,而成人HS的严重程度在不同的致病基因之间没有显着差异。
OBJECTIVE: This study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype-phenotype correlations in Chinese patients with hereditary spherocytosis (HS).
METHODS: Retrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children\'s Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People\'s Hospital and The Third People\'s Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years).
RESULTS: A total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences.
CONCLUSIONS: This study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.