LMX1B基因导致甲髌综合征1例的临床-病理-基因特征分析及文献复习  

Analysis of clinical,pathological and genetic characteristics of LMX1B-induced nail-patella syndrome:A case report and literature review

作　　者：许自川 李悦 杨华彬 邓会英 高霞 Xu Zichuan;Li Yue;Yang Huabin;Deng Huiying;Gao Xia(Department of Nephrology,Liuzhou Hospital,Guangzhou Women and Children's Medical Center,Liuzhou 545000,China;Department of Nephrology,Guangzhou Women and Children’s Medical Center Affiliated to Guangzhou Medical University,Guangzhou 510000,China)

机构地区：[1]广州市妇女儿童医疗中心柳州医院肾内科,广西柳州545000 [2]广州医科大学附属妇女儿童医疗中心肾内科,广东广州510000

出　　处：《临床荟萃》2025年第4期360-365,共6页Clinical Focus

基　　金：广州市科技院校联合项目大黄酸下调足细胞LXR减轻细胞骨架重排缓解蛋白尿的分子机制(20210201022)。

摘　　要：目的甲髌综合征(nail-patella syndrome,NPS)作为多系统受累的罕见疾病,临床诊断困难。本文通过介绍1例NPS儿童的临床、病理及基因型特征,旨在提升对该病的临床诊断能力。方法回顾性分析了广州医科大学附属妇女儿童医疗中心收治的1例以“蛋白尿原因待查”9岁女性患儿病理,总结了该患儿的临床特征、肾脏活检结果及全外显子二代测序数据。结果体格检查发现患儿的体征异常包括:拇指指甲发育不全,尺侧显著,锁骨形态异常,右侧显著伴左肘关节不能外展。实验室检查异常主要有:血清白蛋白水平下降(30.4 g/L),胆固醇水平升高(6.14 mmol/L),肾病水平蛋白尿[55.6 mg/(kg·24h)],伴肾小球源性血尿。肾脏病理显示:光镜未见明显异常,电镜下节段性基底膜内可见胶原样结构,排列紊乱。全外显基因检测:LMX1B基因突变:Exon5,c.755T>Cp.该变异为错义突变:预计会使所编码的蛋白质第252位氨基酸由亮氨酸(Leu)变为脯氨酸(Pro)。出院后3个月随访,尿蛋白波动在+左右,血清白蛋白、胆固醇水平恢复正常。结论对于以肾脏表现为首发症状的患儿,详细的体格检查对发现多系统问题十分重要,基因检测和病理特征对明确NPS的诊断,降低漏诊误诊是非常必要的。Objective Nail-patella syndrome(NPS)is a rare hereditary disease that effects multiple systems and holds great difficulty in the clinical diagnosis.This paper described the clinical features,renal pathology and genotype in a girl with NPS,in order to raise the doctors`vigilance in making the clinical diagnosis of NPS.Methods Pathological data of a 9-year-old girl with proteinuria and admitted in Guangzhou Women and Children’s Medical Center Affiliated to Guangzhou Medical University were retrospectively analyzed.Clinical manifestations,renal biopsy findings and the second-generation whole-exon sequencing data were examined.Results Physical examinations identified development abnormalities,including hypoplasia of thumb nail,abnormal clavicle morphology especially on the right side,and inability to abduct of the left elbow joint.Laboratory abnormalities mainly included decreased serum albumin level(30.4 g/L),increased cholesterol level(6.14 mmol/L),the mass proteinuria(55.6 mg/[kg·24h]),accompanied by glomerular hematuria.Renal pathology showed no obvious damages under light microscope,while much disordered collagen-like structure in the basement membrane was observed under the electron microscope.The second-generation whole-exon sequencing found a missense mutation in the exon 5 of the LMX1B gene(c.755t>CP),where leucine(Leu)at position 252 was altered to proline(Pro).At 3 months of discharge follow-up,the urinary protein fluctuated around+positivity,and the serum albumin and cholesterol returned to normal.Conclusion A detailed physical examination holds great importance for the diagnosis of NPS in children with multi-system abnormality.The gene sequencing and pathological characteristics are necessary to make the diagnosis of NPS and to reduce the misdiagnosis.

关 键 词：甲髌骨综合征 病理 基因 

分 类 号：R681.7[医药卫生—骨科学]