伴發(fā)嚴(yán)重白內(nèi)障的脊髓小腦性共濟(jì)失調(diào)1個家系的臨床表現(xiàn)、影像學(xué)特點(diǎn)及基因突變分析
發(fā)布時間：2018-10-29 15:40
【摘要】：目的：脊髓小腦性共濟(jì)失調(diào)（spinocerebellar ataxia,SCA）是一種少見的神經(jīng)系統(tǒng)退行性疾病。隱襲起病，緩慢進(jìn)展，通常起病后10-20年不能行走。由于SCA癥狀多樣、復(fù)雜且各亞型之間癥狀重疊，造成臨床診斷困難。至今為止各型的診斷仍主要依據(jù)臨床表現(xiàn)，尤其是其特征性臨床表現(xiàn)加上陽性家族史。基因診斷是確診的重要手段�，F(xiàn)有報(bào)道的脊髓小腦性共濟(jì)失調(diào)共有35型，而本研究則發(fā)現(xiàn)了1個伴發(fā)嚴(yán)重白內(nèi)障的脊髓小腦性共濟(jì)失調(diào)（SCA）家系，因此對該家系的臨床表現(xiàn)、影像學(xué)特點(diǎn)及基因突變進(jìn)行研究。 方法：收集該家系臨床資料。采用國際協(xié)作共濟(jì)失調(diào)評估量表（InternationalCooperative Ataxia Rating Scale,ICARS）及簡易智能量表（mini-mental stateexamination,MMSE）對該家族的病例及未發(fā)病者進(jìn)行評分。采用磁共振成像（Magnetic resonance imaging,MRI）對該家系的病例進(jìn)行了顱部掃描，并系統(tǒng)描述這些病例的影像學(xué)變化。采用聚合酶鏈反應(yīng)（polymerase chain reaction,PCR）和瓊脂糖凝膠電泳對該家系中發(fā)病者及部分未發(fā)病者進(jìn)行基因檢測。 結(jié)果：該家系6例發(fā)病者均表現(xiàn)為小腦性共濟(jì)失調(diào)和嚴(yán)重的白內(nèi)障。該家系第2代6人中3人發(fā)病，發(fā)病率為50%，男女均有發(fā)病，家系中6例發(fā)病者平均發(fā)病年齡為27.3（±3.6）歲，3例死亡發(fā)病者的平均病程為14.0（±1.7）年。3例現(xiàn)存發(fā)病者ICARS評分分別為20分、44分、93分，MMSE評分分別為27分、28分、5分。家系中6例發(fā)病者均于20歲后發(fā)病，家系第2、3代平均發(fā)病年齡分別為29.3（±0.6）歲、25.3（±4.5）歲，第3代發(fā)病年齡較第2代提前。該家系2例患者頭MRI均表現(xiàn)為小腦、橋腦萎縮，水平位可見“縱線征”。基因檢測發(fā)現(xiàn)該家系SCA1、SCA2、SCA3、SCA6、SCA7、SCA17、DRPLA基因編碼區(qū)（CAG）n三核苷酸重復(fù)數(shù)目正常；SCA8基因3’非編碼區(qū)（CTG）n三核苷酸重復(fù)數(shù)目正常；SCA12基因5’非編碼區(qū)（CAG）n三核苷酸重復(fù)數(shù)目正常。 結(jié)論：1.本研究發(fā)現(xiàn)大連地區(qū)一個伴發(fā)嚴(yán)重白內(nèi)障的SCA家系，呈常染色體顯性遺傳，，發(fā)病年齡早，進(jìn)展快，晚期出現(xiàn)嚴(yán)重認(rèn)知功能障礙。2.具有明顯的延遲顯性及遺傳早現(xiàn)的遺傳特征，但無明顯的遺傳異質(zhì)性。3.頭MRI可見小腦、橋腦萎縮，水平位可見“縱線征”。4.基因檢測未發(fā)現(xiàn)突變位點(diǎn)，推測該家系可能是一個新型的SCA亞型，也可能是已知的某種SCA亞型，由于遺傳異質(zhì)性而出現(xiàn)新的伴發(fā)癥狀。
[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 (鹵3.6) years, and the incidence of the disease was both male and female, the average age of the 6 cases was 27.3 (鹵3.6) years. The mean course of disease was 14.0 (鹵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 (鹵0.6) years old and 25.3 (鹵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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：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 (鹵3.6) years, and the incidence of the disease was both male and female, the average age of the 6 cases was 27.3 (鹵3.6) years. The mean course of disease was 14.0 (鹵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 (鹵0.6) years old and 25.3 (鹵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.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R744.7;R776.1
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 顧衛(wèi)紅;王國相;王康;孫瑞華;楊斯柳;郝瑩;王桂芳;;脊髓小腦共濟(jì)失調(diào)3型ICARS評分相關(guān)因素分析[J];中國現(xiàn)代神經(jīng)疾病雜志;2008年02期
2 宋e
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