Schimke免疫-骨发育不良5例患儿的临床特征及基因变异分析

doi:10.12372/jcp.2025.25e0144

摘要/Abstract

摘要：

目的总结Schimke免疫-骨发育不良(SIOD)5例患儿的临床特征，分析SMARCAL1基因变异情况，增加对SIOD的认识及了解基因诊断的意义。方法收集2016至2024年于肾内科就诊的5例SIOD患儿的临床资料及基因检测结果。结果例1、例2、例3分别于随访1年、1年3个月、8个月时死亡；例4随访9个月尿蛋白进行性增多，但肾功能正常；例5随访9年，于18岁时出现双髋关节脱位、行髋关节置换手术，目前19岁余，身材矮小、尿蛋白无明显增多、肾功能正常。均进行SMARCAL1基因检测，例1未发现致病变异，例2为c.1334+1G>A、c.1335-2A>C复合杂合剪接变异，例3为c.2425G>A（p.G809R）纯合错义变异，例4为c.1071delT（p.F357LfsTer26）纯合移码变异，例5为c.445C>T（p.Q149X）、c.1933C>T（p.R645C）复合杂合变异。其中c.1334+1G>A、c.2425G>A、c.445C>T、c.1933C>T为已知变异，c.1335-2A>C、c.1071delT为未报道的变异。结论 SIOD患儿临床特征典型，但严重程度各异，基因型与表型严重程度关联尚不明确。及时诊断SIOD可避免激素和免疫抑制剂等的使用，其治疗以对症治疗为主，总体预后不佳。

关键词: Schimke免疫-骨发育不良, 基因变异, SMARCAL1, 儿童

Abstract:

Objective To summarize the clinical characteristics of five children with Schimke immunoosseous dysplasia (SIOD) and analyze the variants in the SMARCAL1 gene, aiming to enhance the understanding of SIOD and underscore the significance of genetic diagnosis. Methods Clinical data and genetic testing results were retrospectively collected from five SIOD patients who presented to the Nephrology Department between 2016 and 2024. Results Patients 1, 2, and 3 died after 1 year, 1 year and 3 months, and 8 months of follow-up, respectively. Patient 4 exhibited progressive proteinuria during 9 months of follow-up but maintained normal renal function. Patient 5 was followed for 9 years; bilateral hip dislocation occurred at the age of 18, for which hip replacement surgery was performed. At 19 years of age, he presented with short stature, stable urinary protein levels, and preserved renal function. All patients underwent sequencing of the SMARCAL1 gene. No pathogenic variant was identified in patient 1. Patient 2 was compound heterozygous for the splice variants c.1334+1G>A and c.1335-2A>C. Patient 3 was homozygous for the missense variant c.2425G>A (p.G809R). Patient 4 was homozygous for the frameshift variant c.1071delT (p.F357LfsTer26). Patient 5 was compound heterozygous for the variants c.445C>T (p.Q149X) and c.1933C>T (p.R645C). Among these, c.1334+1G>A, c.2425G>A, c.445C>T, and c.1933C>T are known pathogenic or likely pathogenic variants, while c.1335-2A>C and c.1071delT represent novel variants not previously reported in the literature. Conclusions SIOD presents with characteristic multisystem clinical features, yet exhibits marked phenotypic variability. The genotype-phenotype correlation remains poorly defined. Early diagnosis enables avoidance of unnecessary immunosuppressive therapies, including corticosteroids, and supports timely symptomatic management. Despite advances in supportive care, the overall prognosis remains poor.

Key words: Schimke immunoosseous dysplasia, variation, SMARCAL1, child

中图分类号:

万灵, 陈朝英, 涂娟, 李华荣, 孙金山. Schimke免疫-骨发育不良5例患儿的临床特征及基因变异分析[J]. 临床儿科杂志, 2025, 43(11): 854-859.

WAN Ling, CHEN Chaoying, TU Juan, LI Huarong, SUN Jinshan. Clinical characteristics and gene variation analysis of 5 Schimke immunoosseous dysplasia children[J]. Journal of Clinical Pediatrics, 2025, 43(11): 854-859.

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患儿	性别	初诊年龄 /岁	初诊身高 /cm	初诊体重 /kg	骨骼影像	免疫缺陷表现	肾脏表现	随访时长	随访结局
例1	男	4.3	86.5(<P₃) 上、下部量未测	12.2 (<P₃)	脊柱短，胸椎椎体扁；双髋臼变浅，双股骨头外上移位	有反复感染 CD3⁺T细胞28% CD3⁺CD4⁺T细胞11% CD3⁺CD8⁺T细胞17%	ALB 28.5 g/L UTP 1.3 g eGFR 165 mL/min/ 1.73 m²	1年	死亡
例2	男	6.6	98(<P₃) 上部量55 下部量43	16.8 (<P₃)	脊柱椎体变扁	无反复感染 CD3⁺T细胞58% CD3⁺CD4⁺T细胞14% CD3⁺CD8⁺T细胞44%	ALB 22.7 g/L UTP 4.5 g eGFR 145 mL/min/ 1.73 m²	1年 3个月	死亡
例3	女	10.8	110(<P₃) 上部量53 下部量57	24.5 (<P₃)	椎体形态不规则，表面凹凸不平，部分椎间隙明显变窄，胸6-8椎体融合；双侧髋臼形态不规则，髋关节间隙变窄，双侧髋臼发育不良?	有反复感染 CD3⁺T细胞43% CD3⁺CD4⁺T细胞14% CD3⁺CD8⁺T细胞27%	ALB 14.6 g/L UTP 9.8 g eGFR 111 mL/min/ 1.73 m²	8个月	死亡
例4	男	5.3	100(<P₃) 上、下部量未测	11 (<P₃)	颈6、7椎体、左侧第3肋、右侧第3、4肋远端形态欠规则；双侧髋臼缘骨结构欠规则	有反复感染 CD3⁺T细胞53% CD3⁺CD4⁺T细胞19% CD3⁺CD8⁺T细胞34%	ALB 25.6 g/L UTP 1.9 g eGFR 144 mL/min/ 1.73 m²	9个月	末次UTP 5 g eGFR 121 mL/ min/1.73 m²
例5	女	10	123(<P₃) 上部量62 下部量61	28 (<P₁₀~ P₂₅)	双侧髋臼形态不规则，髋关节间隙变窄。18岁时双髋关节脱位	无反复感染 CD3⁺T细胞53% CD3⁺CD4⁺T细胞27% CD3⁺CD8⁺T细胞20%	ALB 39.9 g/L UTP 0.7 g eGFR 96 mL/min/ 1.73 m²	9年	身高138 cm （<P₃） UTP 1g eGFR 115 mL/ min/1.73 m²

患儿	核苷酸改变	氨基酸改变	Hom/Het	变异类型	来源	是否为已知突变	ACMG证据	变异评级
例2	c.1334+1G>A c.1335-2A>C	--	Het Het	剪接突变剪接突变	父亲母亲	是否	PVS1+PM2+PM3 PVS1+PM2	P LP
例3	c.2425G>A	p.G809R	Hom	错义突变	父母	是	PM2+PM3+PP3	VUS
例4	c.1071delT	p.F357LfsTer26	Hom	移码突变	父母	否	PVS1+PM2+PM3	P
例5	c.445C>T c.1933C>T	p.Q149X p.R645C	Het Het	无义突变错义突变	父亲母亲	是是	PVS1+PM2 PM1+PM2+PM3+PP3+PS3	LP P