外周血白细胞形态表现为乔丹异常的单纯肌病型中性脂肪沉积症的遗传学分析和文献复习

doi:10.3969/j.issn.1673-8640.2026.10.010

摘要/Abstract

摘要：

目的对1例外周血白细胞形态学表现为乔丹异常的单纯肌病型中性脂肪沉积症（NLSDM）患者的血细胞形态、临床表现、遗传学特征进行分析，并进行文献复习。方法采集NLSDM患者外周血，制备血涂片并观察血细胞形态。采用全外显子测序检测患者的基因变异情况，并通过Sanger测序进行验证，根据美国医学遗传学与基因组学学会（ACMG）指南评估变异的致病性。检索国内外数据库既往报道的NLSDM相关文献，对此类疾病的临床表型和分子遗传学特征进行总结和分析。结果患者表现为不对称肌无力、胰脏和肾脏受累，肾组织存在中性脂肪沉积，白细胞中存在乔丹异常。全外显子测序显示PNPLA2（NM_020376.4）：c.918delG p.A307Pfs*12突变，Sanger测序证实变异存在，患者被确诊为NLSDM。预测PNPLA2 c.918delG p.A307Pfs*12突变会产生缺失COOH端的蛋白或经无义介导的mRNA降解（NMD）。共检索到32篇相关文献，涉及38例NLSDM患者，临床表现异质性较高；血清肌酸激酶（CK）水平升高，行肌肉活检的29例患者中仅1例未检出脂质沉积；行外周血涂片检查的30例患者均发现乔丹异常。38例患者均存在PNPLA2纯和或复合杂合突变，共检出24种基因变异，其中NM_020376.4：c.757+1G>T出现频率最高。结论 NLSDM患者的临床表型异质性较高，易漏诊。外周血涂片中观察到乔丹异常时，应考虑基因突变引起的脂质沉积异常。

关键词: PNPLA2, 乔丹异常, 中性脂肪沉积症

Abstract:

Objective To analyze the peripheral blood morphology，clinical phenotype and genetic features of a patient with neutral lipid storage disease with myopathy（NLSDM） with Jordan's anomaly，and to conduct a literature review. Methods Peripheral blood samples were collected，smears were prepared for morphological evaluation. Whole-exome sequencing was performed on the patient's genomic DNA，and the candidate variant was verified by Sanger sequencing. Pathogenicity was assessed according to the American College of Medical Genetics and Genomics（ACMG） guidelines. A systematic search of domestic and international databases was conducted to review previously reported NLSDM cases，and genotype-phenotype correlations were analyzed. Results The patient presented with asymmetric limb weakness and involvement of the pancreas and kidneys，neutral lipid deposition was demonstrated in multiple organs，and Jordan's anomaly was observed in peripheral blood cells. A homozygous PNPLA2（NM_020376.4）：c.918delG p.A307Pfs*12 was identified，which was predicted to produce a C-terminally truncated protein or to undergo nonsense-mediated mRNA decay（NMD）. A diagnosis of NLSDM was established. A total of 32 publications reporting 38 patients with NLSDM were identified. The clinical manifestations were highly heterogeneous，and elevated serum creatine kinase（CK） levels were commonly observed. Among the 29 patients who underwent muscle biopsy，lipid deposition was determined in all but 1 patient. Jordan's anomaly was identified in all 30 patients who underwent peripheral blood smear examination. All the 38 patients harbored either homozygous or compound heterozygous variants in PNPLA2. A total of 24 distinct PNPLA2 variants were identified，of which NM_020376.4：c.757+1G>T was the most frequently determined. Conclusions NLSDM is a rare autosomal recessive disorder with marked phenotypic heterogeneity and is easily under-recognized. The presence of Jordan's anomaly in blood smears should alert clinicians to underlying genetic disturbances of lipid metabolism and prompt appropriate molecular investigations.

Key words: PNPLA2, Jordan's anomaly, Neutral lipid storage disease with myopathy

中图分类号:

R446.7

黄之玺, 郭平, 王剑飚, 杨铭康, 华任翔, 周嘉宽, 薛伊伦, 蔡祺. 外周血白细胞形态表现为乔丹异常的单纯肌病型中性脂肪沉积症的遗传学分析和文献复习[J]. 检验医学, 2026, 41(10): 997-1003.

HUANG Zhixi, GUO Ping, WANG Jianbiao, YANG Mingkang, HUA Renxiang, ZHOU Jiakuan, XUE Yilun, CAI Qi. Genetic analysis and literature review of neutral lipid storage disease with myopathy with Jordan's anomaly[J]. Laboratory Medicine, 2026, 41(10): 997-1003.

图/表 5

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