Abstract：
Mucopolysaccharidosis type IIIC (MPS IIIC; Sanfilippo syndrome C) is a rare lysosomal storage disease caused by mutations in the heparan-α-glucosaminide N-acetyltransferase (HGSNAT) gene, resulting in the accumulation of heparan sulfate. MPS IIIC is characterized by severe neuropsychiatric symptoms and mild somatic symptoms.
Our study analyzed the clinical presentation and biochemical characteristics of ten Chinese MPS IIIC patients from eight families. Whole exome sequencing was applied to identify the variants in HGSNAT gene. In one patient with only one mutant allele identified firstly, whole genome sequencing was applied. The pathogenic effect of novel variants was evaluated in silico.
The mean age at the onset of clinical symptoms was 4.2 ± 2.5 years old, and the mean age of diagnosis was 7.6 ± 4.5 years old, indicating a delay of diagnosis. The most common onset symptoms were speech deterioration, and the most frequent presenting symptoms are speech deterioration, mental deterioration, hyperactivity and hepatomegaly, sequentially. All mutant alleles of 10 patients have been identified. There were eleven different HGSNAT variants, and the most common one was a previously reported variant c.493 + 1G > A. There were six novel variants, p.R124T, p.G290A, p.G426E, c.743 + 101_743 + 102delTT, c.851 + 171T > A and p.V582Yfs*18 in our cohort. Extraordinarily, two deep intron variants were identified in our cohort, with the variant c.851 + 171T > A identified by whole genome sequencing.
This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients, which would assist in the early diagnosis and genetic counselling of MPS IIIC.
Our study analyzed the clinical presentation and biochemical characteristics of ten Chinese MPS IIIC patients from eight families. Whole exome sequencing was applied to identify the variants in HGSNAT gene. In one patient with only one mutant allele identified firstly, whole genome sequencing was applied. The pathogenic effect of novel variants was evaluated in silico.
The mean age at the onset of clinical symptoms was 4.2 ± 2.5 years old, and the mean age of diagnosis was 7.6 ± 4.5 years old, indicating a delay of diagnosis. The most common onset symptoms were speech deterioration, and the most frequent presenting symptoms are speech deterioration, mental deterioration, hyperactivity and hepatomegaly, sequentially. All mutant alleles of 10 patients have been identified. There were eleven different HGSNAT variants, and the most common one was a previously reported variant c.493 + 1G > A. There were six novel variants, p.R124T, p.G290A, p.G426E, c.743 + 101_743 + 102delTT, c.851 + 171T > A and p.V582Yfs*18 in our cohort. Extraordinarily, two deep intron variants were identified in our cohort, with the variant c.851 + 171T > A identified by whole genome sequencing.
This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients, which would assist in the early diagnosis and genetic counselling of MPS IIIC.
摘要：
背景：粘多糖贮积症IIIC型（MPSIIIC；Sanfilippo综合征C）是一种罕见的溶酶体贮积病，由乙酰肝素-α-氨基葡萄糖胺N-乙酰转移酶（HGSNAT）基因突变引起，导致硫酸乙酰肝素的积累。MPSIIIC的特征是严重的神经精神症状和轻度的躯体症状。
方法：我们的研究分析了来自8个家庭的10名中国MPSIIIC患者的临床表现和生化特征。应用全外显子组测序来鉴定HGSNAT基因中的变体。在一个只有一个突变等位基因的患者中，应用全基因组测序。在计算机上评估了新变体的致病作用。
结果：临床症状发作的平均年龄为4.2±2.5岁，诊断平均年龄为7.6±4.5岁，表明诊断延迟。最常见的症状是言语恶化，最常见的症状是言语恶化，精神恶化,多动症和肝肿大，顺序。已经鉴定了10名患者的所有突变等位基因。有11种不同的HGSNAT变体，最常见的是以前报道的变体c.493+1G>A。有六个新的变体，p.R124T,p.G290A,p.G426E,c.743+101_743+102delTT,c.851+171T>A和p.V582Yfs*18在我们的队列中。非常，在我们的队列中发现了两个深层内含子变异，通过全基因组测序鉴定出变异c.851+171T>A。
结论：本研究分析了临床，生物化学，和10名中国MPSIIIC患者的遗传特征，这将有助于MPSIIIC的早期诊断和遗传咨询。
方法：我们的研究分析了来自8个家庭的10名中国MPSIIIC患者的临床表现和生化特征。应用全外显子组测序来鉴定HGSNAT基因中的变体。在一个只有一个突变等位基因的患者中，应用全基因组测序。在计算机上评估了新变体的致病作用。
结果：临床症状发作的平均年龄为4.2±2.5岁，诊断平均年龄为7.6±4.5岁，表明诊断延迟。最常见的症状是言语恶化，最常见的症状是言语恶化，精神恶化,多动症和肝肿大，顺序。已经鉴定了10名患者的所有突变等位基因。有11种不同的HGSNAT变体，最常见的是以前报道的变体c.493+1G>A。有六个新的变体，p.R124T,p.G290A,p.G426E,c.743+101_743+102delTT,c.851+171T>A和p.V582Yfs*18在我们的队列中。非常，在我们的队列中发现了两个深层内含子变异，通过全基因组测序鉴定出变异c.851+171T>A。
结论：本研究分析了临床，生物化学，和10名中国MPSIIIC患者的遗传特征，这将有助于MPSIIIC的早期诊断和遗传咨询。
