Zuo Hanheng, Li Yinping, Cui Yinghua, Zhang Jinguo, Shen Caiyun, Zhu Wenya, Du Chunlei
Department of Cardiology, the Affiliated Hospital of Jining Medical University, Shandong Provincial Key Laboratory for the Diagnosis and Treatment of Cardiac Diseases, Jining, Shandong 272029, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Apr 10;40(4):452-457. doi: 10.3760/cma.j.cn511374-20221107-00766.
To explore the clinical and genetic characteristics of a patient with hypertrophic cardiomyopathy as the initial manifestation of Mucopolysaccharidosis type Ⅲ A (MPS Ⅲ A).
A female patient with MPS Ⅲ A who was admitted to the Affiliated Hospital of Jining Medical University in January 2022 and her family members (seven individuals from three generations) were selected as the study subjects. Clinical data of the proband were collected. Peripheral blood samples of the proband was collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. Heparan-N-sulfatase activity was determined for the disease associated with the variant site.
The proband was a 49-year-old woman, for whom cardiac MRI has revealed significant thickening (up to 20 mm) of left ventricular wall and delayed gadolinium enhancement at the apical myocardium. Genetic testing revealed that she has harbored compound heterozygous variants in exon 17 of the SGSH gene, namely c.545G>A (p.Arg182His) and c.703G>A (p.Asp235Asn). Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PM2_Supporting +PM3+PP1Strong+PP3+PP4; PS3+PM1+PM2_Supporting +PM3+PP3+PP4). Sanger sequencing confirmed that her mother was heterozygous for the c.545G>A (p.Arg182His) variant, whilst her father, sisters and her son were heterozygous for the c.703G>A (p.Asp235Asn) variant. Determination of blood leukocyte heparan-N-sulfatase activity suggested that the patient had a low level of 1.6 nmol/(g·h), whilst that of her father, elder and younger sisters and son were all in the normal range.
The compound heterozygous variants of the SGSH gene probably underlay the MPS ⅢA in this patient, for which hypertrophic cardiomyopathy is an associated phenotype.
探讨以肥厚型心肌病为初始表现的ⅢA型黏多糖贮积症（MPSⅢA）患者的临床及遗传特征。
选取2022年1月入住济宁医学院附属医院的1例MPSⅢA女性患者及其家庭成员（三代7人）作为研究对象。收集先证者的临床资料。采集先证者外周血样本并进行全外显子组测序。通过Sanger测序验证候选变异。测定与变异位点相关疾病的硫酸乙酰肝素N - 硫酸酯酶活性。
先证者为一名49岁女性，心脏磁共振成像显示左心室壁显著增厚（达20mm），心尖心肌钆延迟强化。基因检测显示，她在SGSH基因第17外显子存在复合杂合变异，即c.545G>A（p.Arg182His）和c.703G>A（p.Asp235Asn）。根据美国医学遗传学与基因组学学会（ACMG）指南，这两个变异均被预测为致病性变异（PM2_Supporting +PM3+PP1Strong+PP3+PP4；PS3+PM1+PM2_Supporting +PM3+PP3+PP4）。Sanger测序证实，其母亲为c.545G>A（p.Arg182His）变异的杂合子，而其父亲、姐妹及儿子为c.703G>A（p.Asp235Asn）变异的杂合子。血液白细胞硫酸乙酰肝素N - 硫酸酯酶活性测定显示，患者活性水平较低，为1.6 nmol/（g·h），而其父亲、姐姐、妹妹及儿子的活性均在正常范围内。
SGSH基因的复合杂合变异可能是该患者MPSⅢA的病因，肥厚型心肌病是其相关表型。
