伴发严重白内障的脊髓小脑性共济失调1个家系的临床表现、影像学特点及基因突变分析
发布时间：2018-10-29 15:40
【摘要】：目的：脊髓小脑性共济失调（spinocerebellar ataxia,SCA）是一种少见的神经系统退行性疾病。隐袭起病，缓慢进展，通常起病后10-20年不能行走。由于SCA症状多样、复杂且各亚型之间症状重叠，造成临床诊断困难。至今为止各型的诊断仍主要依据临床表现，尤其是其特征性临床表现加上阳性家族史。基因诊断是确诊的重要手段。现有报道的脊髓小脑性共济失调共有35型，而本研究则发现了1个伴发严重白内障的脊髓小脑性共济失调（SCA）家系，因此对该家系的临床表现、影像学特点及基因突变进行研究。 方法：收集该家系临床资料。采用国际协作共济失调评估量表（InternationalCooperative Ataxia Rating Scale,ICARS）及简易智能量表（mini-mental stateexamination,MMSE）对该家族的病例及未发病者进行评分。采用磁共振成像（Magnetic resonance imaging,MRI）对该家系的病例进行了颅部扫描，并系统描述这些病例的影像学变化。采用聚合酶链反应（polymerase chain reaction,PCR）和琼脂糖凝胶电泳对该家系中发病者及部分未发病者进行基因检测。 结果：该家系6例发病者均表现为小脑性共济失调和严重的白内障。该家系第2代6人中3人发病，发病率为50%，男女均有发病，家系中6例发病者平均发病年龄为27.3（±3.6）岁，3例死亡发病者的平均病程为14.0（±1.7）年。3例现存发病者ICARS评分分别为20分、44分、93分，MMSE评分分别为27分、28分、5分。家系中6例发病者均于20岁后发病，家系第2、3代平均发病年龄分别为29.3（±0.6）岁、25.3（±4.5）岁，第3代发病年龄较第2代提前。该家系2例患者头MRI均表现为小脑、桥脑萎缩，水平位可见“纵线征”。基因检测发现该家系SCA1、SCA2、SCA3、SCA6、SCA7、SCA17、DRPLA基因编码区（CAG）n三核苷酸重复数目正常；SCA8基因3’非编码区（CTG）n三核苷酸重复数目正常；SCA12基因5’非编码区（CAG）n三核苷酸重复数目正常。 结论：1.本研究发现大连地区一个伴发严重白内障的SCA家系，呈常染色体显性遗传，，发病年龄早，进展快，晚期出现严重认知功能障碍。2.具有明显的延迟显性及遗传早现的遗传特征，但无明显的遗传异质性。3.头MRI可见小脑、桥脑萎缩，水平位可见“纵线征”。4.基因检测未发现突变位点，推测该家系可能是一个新型的SCA亚型，也可能是已知的某种SCA亚型，由于遗传异质性而出现新的伴发症状。
[Abstract]:Objective: Spinal cerebellar ataxia (spinocerebellar ataxia,SCA) is a rare neurodegenerative disease. Onset, slow progression, usually 10-20 years after the onset of the disease can not walk. The clinical diagnosis of SCA is difficult because of its variety of symptoms, complexity and overlap of symptoms among subtypes. So far, the diagnosis of various types is still based on clinical manifestations, especially its characteristic clinical manifestations plus positive family history. Genetic diagnosis is an important means of diagnosis. There are 35 types of spinal cerebellar ataxia reported in the present study, and a (SCA) family with severe cataract was found in this study. Imaging features and gene mutation were studied. Methods: the clinical data of the family were collected. (InternationalCooperative Ataxia Rating Scale,ICARS and mini-mental stateexamination,MMSE were used to evaluate the family cases and patients without disease. Magnetic resonance imaging (Magnetic resonance imaging,MRI) was used to scan the cranial part of the family, and the imaging changes were described systematically. Polymerase chain reaction (polymerase chain reaction,PCR) and agarose gel electrophoresis (agarose gel electrophoresis) were used to detect the genes of the patients and part of the patients. Results: all 6 cases of this family showed cerebellar ataxia and severe cataract. In this family, 3 out of 6 people of the second generation had the disease, the incidence rate was 50. The average age of the 6 cases in the family was 27.3 (卤3.6) years, and the incidence of the disease was both male and female, the average age of the 6 cases was 27.3 (卤3.6) years. The mean course of disease was 14.0 (卤1.7) years in 3 dead patients, the ICARS scores were 20, 44, 93, and the MMSE scores were 27, 28 and 5, respectively. The mean age of onset of the third generation was 29.3 (卤0.6) years old and 25.3 (卤4.5) years old, respectively. The onset age of the third generation was earlier than that of the second generation. In this pedigree, MRI showed cerebellum and pons atrophy, and "longitudinal sign" was observed in horizontal position. The number of (CAG) n trinucleotide repeats in the coding region of SCA1,SCA2,SCA3,SCA6,SCA7,SCA17,DRPLA gene and (CTG) n trinucleotide repeats in the 3 'non-coding region of SCA8 gene were normal. The number of (CAG) n trinucleotide repeats in 5'- non-coding region of SCA12 gene was normal. Conclusion 1. In this study, we found that a SCA family with severe cataract in Dalian area was autosomal dominant, with early onset age, rapid progression and severe cognitive impairment at the late stage. 2. There were obvious genetic characteristics of delayed dominance and genetic preexisting, but no obvious genetic heterogeneity. MRI showed cerebellum, pons atrophy and horizontal "longitudinal sign". 4. 4. No mutation loci were found in the genetic analysis. It is speculated that the family may be a new SCA subtype or a known SCA subtype, with new syndromes due to genetic heterogeneity.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R744.7;R776.1
[Abstract]:Objective: Spinal cerebellar ataxia (spinocerebellar ataxia,SCA) is a rare neurodegenerative disease. Onset, slow progression, usually 10-20 years after the onset of the disease can not walk. The clinical diagnosis of SCA is difficult because of its variety of symptoms, complexity and overlap of symptoms among subtypes. So far, the diagnosis of various types is still based on clinical manifestations, especially its characteristic clinical manifestations plus positive family history. Genetic diagnosis is an important means of diagnosis. There are 35 types of spinal cerebellar ataxia reported in the present study, and a (SCA) family with severe cataract was found in this study. Imaging features and gene mutation were studied. Methods: the clinical data of the family were collected. (InternationalCooperative Ataxia Rating Scale,ICARS and mini-mental stateexamination,MMSE were used to evaluate the family cases and patients without disease. Magnetic resonance imaging (Magnetic resonance imaging,MRI) was used to scan the cranial part of the family, and the imaging changes were described systematically. Polymerase chain reaction (polymerase chain reaction,PCR) and agarose gel electrophoresis (agarose gel electrophoresis) were used to detect the genes of the patients and part of the patients. Results: all 6 cases of this family showed cerebellar ataxia and severe cataract. In this family, 3 out of 6 people of the second generation had the disease, the incidence rate was 50. The average age of the 6 cases in the family was 27.3 (卤3.6) years, and the incidence of the disease was both male and female, the average age of the 6 cases was 27.3 (卤3.6) years. The mean course of disease was 14.0 (卤1.7) years in 3 dead patients, the ICARS scores were 20, 44, 93, and the MMSE scores were 27, 28 and 5, respectively. The mean age of onset of the third generation was 29.3 (卤0.6) years old and 25.3 (卤4.5) years old, respectively. The onset age of the third generation was earlier than that of the second generation. In this pedigree, MRI showed cerebellum and pons atrophy, and "longitudinal sign" was observed in horizontal position. The number of (CAG) n trinucleotide repeats in the coding region of SCA1,SCA2,SCA3,SCA6,SCA7,SCA17,DRPLA gene and (CTG) n trinucleotide repeats in the 3 'non-coding region of SCA8 gene were normal. The number of (CAG) n trinucleotide repeats in 5'- non-coding region of SCA12 gene was normal. Conclusion 1. In this study, we found that a SCA family with severe cataract in Dalian area was autosomal dominant, with early onset age, rapid progression and severe cognitive impairment at the late stage. 2. There were obvious genetic characteristics of delayed dominance and genetic preexisting, but no obvious genetic heterogeneity. MRI showed cerebellum, pons atrophy and horizontal "longitudinal sign". 4. 4. No mutation loci were found in the genetic analysis. It is speculated that the family may be a new SCA subtype or a known SCA subtype, with new syndromes due to genetic heterogeneity.
【学位授予单位】：大连医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R744.7;R776.1
【参考文献】
相关期刊论文 前2条
1 顾卫红;王国相;王康;孙瑞华;杨斯柳;郝莹;王桂芳;;脊髓小脑共济失调3型ICARS评分相关因素分析[J];中国现代神经疾病杂志;2008年02期
2 宋e
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