ALMS1复合杂合变异致Alstrom综合征一例

doi:10.12280/gjszjk.20250132

国际生殖健康/计划生育杂志 ›› 2025, Vol. 44 ›› Issue (6): 459-463.doi: 10.12280/gjszjk.20250132

ALMS1复合杂合变异致Alstrom综合征一例

陈慧芳, 左文涛, 赵灵芝, 陈进凡, 惠玲(), 张钏()

730050 兰州，甘肃省中医院输血科（陈慧芳，左文涛，赵灵芝，陈进凡）；甘肃省妇幼保健院（甘肃省中心医院）医学遗传中心，甘肃省出生缺陷与罕见病临床研究中心（陈慧芳，惠玲，张钏）

收稿日期:2025-03-20 出版日期:2025-11-15 发布日期:2025-11-18
通讯作者: 惠玲，E-mail：1065753301@qq.com；张钏，E-mail：zhangchuan0404@163.com
基金资助:
甘肃省科技厅创新基地及人才计划(21JR7RA680);兰州市科技计划项目(2021-1-182);国家科技资源共享服务平台计划项目(YCZYPT[2020]05-03)

A Case of ALMS1 Compound Heterozygous Variant Causing Alstrom Syndrome

CHEN Hui-fang, ZUO Wen-tao, ZHAO Ling-zhi, CHEN Jin-fan, HUI Ling(), ZHANG Chuan()

Department of Transfusion, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China (CHEN Hui-fang, ZUO Wen-tao, ZHAO Ling-zhi, CHEN Jin-fan); Medical Genetics Center, Gansu Provincial Clinical Research Center for Birth Defects and Rare Diseases, Gansu Provincial Maternity and Child Health Hospital (Gansu Province Central Hospital), Lanzhou 730050, China (CHEN Hui-fang, HUI Ling, ZHANG Chuan)

Received:2025-03-20 Published:2025-11-15 Online:2025-11-18
Contact: HUI Ling, E-mail: 1065753301@qq.com;ZHANG Chuan, E-mail: zhangchuan0404@163.com

摘要/Abstract

摘要：

Alstrom综合征是一种累及多系统的常染色体隐性遗传病，由ALMS1变异所致。该病发病机制尚不完全明确，缺乏有效的治疗手段且预后差。临床上该病患者发病年龄小，临床症状范围广，病情严重程度不一，这为该病的诊疗带来了困难。报告1例利用全外显子组测序（whole exome sequencing，WES）技术最终确诊的Alstrom综合征患者情况，该患者表现为充血性心力衰竭、先天性心肌病、房间隔缺损、生长发育迟缓及反复发作的肺炎，给予控制感染、强心、利尿和补钙等对症治疗，其最终预后差。经WES检测发现的ALMS1复合杂合变异c.11647_c.11648delAT(p.M3883fs*9)/c.2888_c.2897delGTGTTTTCTA(p.S963fs*15)为罕见变异。该复合杂合变异的发现为Alstrom综合征的遗传学研究提供了新的参考。

关键词: Alstrom综合征, 全外显子组测序, 心力衰竭, 肺炎, ALMS1

Abstract:

Alstrom syndrome is an autosomal recessive disorder with multisystem involvement caused by the mutations in ALMS1 gene. The pathogenesis of the disease is not fully understood, the effective treatment is also lacking, and the prognosis is poor. The young age of onset, wide range of clinical symptoms and varying severity of the disease make it difficult to diagnose and treat. We report a female case of Alstrom syndrome diagnosed by whole exome sequencing (WES). The patient presented with congestive heart failure, congenital cardiomyopathy, atrial septal defect, growth retardation and recurrent pneumonia. She was given symptomatic treatments including infection control, cardiotonic, diuretic, and calcium supplementation, but the final prognosis was poor. The ALMS1 compound heterozygous variant c.11647_c.11648delAT (p.M3883fs*9)/ c.2888_c.2897del GTGTTTTCTA (p.S963fs*15) was found to be a rare variant. The discovery of this compound heterozygous variant provided a new reference for the genetic study of Alstrom syndrome.

Key words: Alstrom syndrome, Whole exome sequencing, Heart failure, Pneumonia, ALMS1

陈慧芳, 左文涛, 赵灵芝, 陈进凡, 惠玲, 张钏. ALMS1复合杂合变异致Alstrom综合征一例[J]. 国际生殖健康/计划生育杂志, 2025, 44(6): 459-463.

CHEN Hui-fang, ZUO Wen-tao, ZHAO Ling-zhi, CHEN Jin-fan, HUI Ling, ZHANG Chuan. A Case of ALMS1 Compound Heterozygous Variant Causing Alstrom Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2025, 44(6): 459-463.

图/表 3

图1 患者心脏彩色多普勒超声检查图注：A 卵圆孔未闭状态；B 心内膜弹力纤维增生；C 二、三尖瓣探及中-大量反流信号，二尖瓣反流速度242 cm/s，三尖瓣反流速度286 cm/s

图2 胸部正位数字化X线摄影图注：双肺纹理增重，心影增大

图3 患者家系Sanger测序图注：箭头所示为变异位点。

参考文献 16

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ALMS1复合杂合变异致Alstrom综合征一例

A Case of ALMS1 Compound Heterozygous Variant Causing Alstrom Syndrome

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