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Abstract：
BACKGROUND: Alström syndrome (AS) is a rare autosomal recessive disorder that leads to multiple organ fibrosis and failure. Precise diagnosis from the clinical symptoms is challenging due to its highly variabilities and its frequent confusion with other ciliopathies and genetic diseases. Currently, mutations in the ALMS1 gene have been reported as a major cause of AS, thus, it is crucial to focus on the detection and discovery of ALMS1 mutations.
METHODS: We present a case of a 13-year-old Chinese boy weighing 70 kg and standing 168 cm tall. He has two younger brothers. Their parents hail from different ancestral homes in eastern and northern China. The patient\'s primary clinical findings included visual impairment at the age of four and progressive hearing loss starting at the age of ten. Subsequently, at the age of twelve, the patient developed hyperlipidaemia and hyperinsulinemia. Ultrasonographic findings indicated the presence of gallstones and mild fatty liver. His Body Mass Index (BMI) significantly increased to 25 kg/m2 (ref: 18.5-23.9 kg/m2). Additionally, echocardiography revealed mild mitral and tricuspid regurgitation. Ultimately, Whole Exome Sequencing (WES) identified a new missense mutation in the ALMS1 gene (NG_011690.1 (NM_015120): c.9536G > A (p.R3179Q)). This missense mutation generated an aberrant splicer and disrupted the stability and hydrophobicity of proteins, which preliminarily determined as \" likely pathogenic\". Therefore, considering all the above symptoms and molecular analysis, we deduced that the patient was diagnosed with AS according to the guidelines. We recommended that he continue wearing glasses and undergo an annual physical examination.
CONCLUSIONS: In this case report, we report a novel homozygous ALMS1 mutation associated with AS in the Chinese population, which expands the mutation spectrum of ALMS1. Genetic testing indeed should be incorporated into the diagnosis of syndromic deafness, as it can help avoid misdiagnoses of AS. While there is no specific treatment for AS, early diagnosis and intervention can alleviate the progression of some symptoms and improve patients\' quality of life.
METHODS: We present a case of a 13-year-old Chinese boy weighing 70 kg and standing 168 cm tall. He has two younger brothers. Their parents hail from different ancestral homes in eastern and northern China. The patient\'s primary clinical findings included visual impairment at the age of four and progressive hearing loss starting at the age of ten. Subsequently, at the age of twelve, the patient developed hyperlipidaemia and hyperinsulinemia. Ultrasonographic findings indicated the presence of gallstones and mild fatty liver. His Body Mass Index (BMI) significantly increased to 25 kg/m2 (ref: 18.5-23.9 kg/m2). Additionally, echocardiography revealed mild mitral and tricuspid regurgitation. Ultimately, Whole Exome Sequencing (WES) identified a new missense mutation in the ALMS1 gene (NG_011690.1 (NM_015120): c.9536G > A (p.R3179Q)). This missense mutation generated an aberrant splicer and disrupted the stability and hydrophobicity of proteins, which preliminarily determined as \" likely pathogenic\". Therefore, considering all the above symptoms and molecular analysis, we deduced that the patient was diagnosed with AS according to the guidelines. We recommended that he continue wearing glasses and undergo an annual physical examination.
CONCLUSIONS: In this case report, we report a novel homozygous ALMS1 mutation associated with AS in the Chinese population, which expands the mutation spectrum of ALMS1. Genetic testing indeed should be incorporated into the diagnosis of syndromic deafness, as it can help avoid misdiagnoses of AS. While there is no specific treatment for AS, early diagnosis and intervention can alleviate the progression of some symptoms and improve patients\' quality of life.
摘要：
背景：Alström综合征（AS）是一种罕见的常染色体隐性遗传疾病，可导致多器官纤维化和衰竭。由于其高度变异性以及与其他纤毛病和遗传疾病的频繁混淆，从临床症状进行精确诊断具有挑战性。目前,ALMS1基因突变已被报道为AS的主要原因，因此，重点是ALMS1突变的检测和发现。
方法：我们介绍了一个13岁的中国男孩，体重70公斤，身高168厘米。他有两个弟弟。他们的父母来自中国东部和北部不同的祖先家园。患者的主要临床发现包括4岁时的视力障碍和10岁时开始的进行性听力损失。随后，十二岁的时候,患者出现高脂血症和高胰岛素血症.超声检查结果表明存在胆结石和轻度脂肪肝。他的身体质量指数（BMI）显着增加到25kg/m2（编号：18.5-23.9kg/m2）。此外,超声心动图显示轻度二尖瓣和三尖瓣反流。最终,全外显子组测序（WES）鉴定了ALMS1基因中的新错义突变（NG_011690.1（NM_015120）：c.9536G>A（p。R3179Q))。这种错义突变产生了异常的剪接剂，破坏了蛋白质的稳定性和疏水性，初步确定为“可能致病”。因此,考虑到上述所有症状和分子分析，根据指南,我们推断患者被诊断为AS.我们建议他继续戴眼镜并接受年度体检。
结论：在本案例报告中，我们报道了一个新的与中国人群AS相关的纯合ALMS1突变，这扩展了ALMS1的突变谱。基因检测确实应该纳入综合征性耳聋的诊断，因为它可以帮助避免AS的误诊。虽然没有针对AS的特定治疗方法，早期诊断和干预可以缓解某些症状的进展，提高患者的生活质量。
方法：我们介绍了一个13岁的中国男孩，体重70公斤，身高168厘米。他有两个弟弟。他们的父母来自中国东部和北部不同的祖先家园。患者的主要临床发现包括4岁时的视力障碍和10岁时开始的进行性听力损失。随后，十二岁的时候,患者出现高脂血症和高胰岛素血症.超声检查结果表明存在胆结石和轻度脂肪肝。他的身体质量指数（BMI）显着增加到25kg/m2（编号：18.5-23.9kg/m2）。此外,超声心动图显示轻度二尖瓣和三尖瓣反流。最终,全外显子组测序（WES）鉴定了ALMS1基因中的新错义突变（NG_011690.1（NM_015120）：c.9536G>A（p。R3179Q))。这种错义突变产生了异常的剪接剂，破坏了蛋白质的稳定性和疏水性，初步确定为“可能致病”。因此,考虑到上述所有症状和分子分析，根据指南,我们推断患者被诊断为AS.我们建议他继续戴眼镜并接受年度体检。
结论：在本案例报告中，我们报道了一个新的与中国人群AS相关的纯合ALMS1突变，这扩展了ALMS1的突变谱。基因检测确实应该纳入综合征性耳聋的诊断，因为它可以帮助避免AS的误诊。虽然没有针对AS的特定治疗方法，早期诊断和干预可以缓解某些症状的进展，提高患者的生活质量。
