PDF(Pubmed)
Abstract：
BACKGROUND: Wolfram syndrome is a rare autosomal recessive neurodegenerative disorder that affects 1/200,000 to 1/1,000,000 children. It is characterized by juvenile onset diabetes, optic nerve atrophy and other systemic manifestations. Symptoms of the disease arise mostly in early childhood with a high mortality rate due to severe neurological complications. Two causative genes have been identifed in this syndrome; the classical form is caused by autosomal recessive mutations of the WFS1 gene, and a smaller portion of patients has mutations in the CIDS2 gene, which are responsible for autosomal recessive Wolfram syndrome 2.
METHODS: We report the case of a 28-year-old Moroccan boy born from consanguineous parents referred to the department of medical genetics at the National Institute of Health in Rabat. The diagnosis of Wolfram syndrome was made based on insulin-dependent diabetes, optic nerve atrophy, sensorineural deafness, urological abnormalities and psychiatric illness. To establish the diagnosis at a molecular level, we performed next-generation sequencing in the index patient, which revealed compound heterozygous WFS1 mutations: c.1113G > A (p.Trp371Ter) and c.1223_1224insGGAACCACCTGGAGCCCTATGCCCATTT (p.Phe408fs). This second variant has never been described in patients with Wolfram syndrome.
CONCLUSIONS: The identification of the genetic substrate in our patient confirmed the clinical diagnosis of Wolfram syndrome and allowed us to provide him an appropriate management and genetic counseling to his family.
METHODS: We report the case of a 28-year-old Moroccan boy born from consanguineous parents referred to the department of medical genetics at the National Institute of Health in Rabat. The diagnosis of Wolfram syndrome was made based on insulin-dependent diabetes, optic nerve atrophy, sensorineural deafness, urological abnormalities and psychiatric illness. To establish the diagnosis at a molecular level, we performed next-generation sequencing in the index patient, which revealed compound heterozygous WFS1 mutations: c.1113G > A (p.Trp371Ter) and c.1223_1224insGGAACCACCTGGAGCCCTATGCCCATTT (p.Phe408fs). This second variant has never been described in patients with Wolfram syndrome.
CONCLUSIONS: The identification of the genetic substrate in our patient confirmed the clinical diagnosis of Wolfram syndrome and allowed us to provide him an appropriate management and genetic counseling to his family.
摘要：
背景：Wolfram综合征是一种罕见的常染色体隐性遗传神经退行性疾病，影响1/200,000至1/1,000,000儿童。它的特点是青少年发病的糖尿病，视神经萎缩等全身表现。该疾病的症状主要出现在儿童早期，由于严重的神经系统并发症，死亡率很高。在该综合征中已鉴定出两个致病基因；经典形式是由WFS1基因的常染色体隐性突变引起的，一小部分患者的CIDS2基因突变，常染色体隐性遗传Wolfram综合征2。
方法：我们报告了一例28岁的摩洛哥男孩，该男孩来自父母的近亲，转诊至拉巴特国立卫生研究院医学遗传学系。Wolfram综合征的诊断是基于胰岛素依赖型糖尿病，视神经萎缩,感觉神经性耳聋,泌尿系统异常和精神疾病。为了在分子水平上建立诊断，我们在索引患者中进行了下一代测序，揭示了复合杂合WFS1突变：c.1113G>A（p。Trp371Ter）和c.1223_1224insGGACACCACCTGGAGCCCTATGCCCATT（第Phe408fs)。在Wolfram综合征患者中从未描述过第二种变体。
结论：对我们患者遗传底物的鉴定证实了Wolfram综合征的临床诊断，并使我们能够为他的家人提供适当的管理和遗传咨询。
方法：我们报告了一例28岁的摩洛哥男孩，该男孩来自父母的近亲，转诊至拉巴特国立卫生研究院医学遗传学系。Wolfram综合征的诊断是基于胰岛素依赖型糖尿病，视神经萎缩,感觉神经性耳聋,泌尿系统异常和精神疾病。为了在分子水平上建立诊断，我们在索引患者中进行了下一代测序，揭示了复合杂合WFS1突变：c.1113G>A（p。Trp371Ter）和c.1223_1224insGGACACCACCTGGAGCCCTATGCCCATT（第Phe408fs)。在Wolfram综合征患者中从未描述过第二种变体。
结论：对我们患者遗传底物的鉴定证实了Wolfram综合征的临床诊断，并使我们能够为他的家人提供适当的管理和遗传咨询。
